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Moderna is announcing three new vaccine programs (modernatx.com)
357 points by Osiris30 10 days ago | hide | past | favorite | 232 comments

One of these is for the little known Nipah virus. This virus is really scary. Like the Coronavirus, it jumps to humans from bats. Unlike the Coronavirus, it is extremely lethal. In the last outbreak, in 2018 [1], the case fatality rate was 89%. Fortunately, there were only 19 cases (17 died).

[1] https://en.wikipedia.org/wiki/2018_Nipah_virus_outbreak_in_K...

Is my understanding correct that a virus so deadly would quickly peter out because it kills its hosts before it can spread?

That's my understanding as well. The problem, though, is that the virus doesn't completely peter out because it survives in the bats. There is a possibility a mutation makes the virus less lethal, in which case it could cause much more problems when it jumps again from bat to human. Maybe next year, maybe in a hundred years, maybe never.

Disclaimer: I'm absolutely no expert. The above is only my best guess.

It probably could also mutate in a way that it would be just as lethal, but with a longer incubation period.

Yeah. We all played that scenario on Plague!

It also depends on how long it stays asymptomatic (so that a host can go around and infect other people before dying) and how well it spreads from host to host, and probably other factors that I don't know about

AIDS, for instance, also had an extremely high case fatality rate before modern treatment but due to it's slow progression it can spread just fine.


btw, maybe moderna can go after AIDS sometime later? I wonder how mRNA vaccines will work for AIDS patients...

HIV is one of the three new programs in this announcement. So yes, that's precisely what they're hoping.

(Pedantry: HIV is the virus that causes the disease AIDS. The goal is to prevent AIDS by vaccinating against HIV. It's unlikely that the vaccine would be able to help patients who already have AIDS.)

damn I have a habit of only reading HN comments and guessing what the article is about

It is slightly odd that the headline doesn't feature HIV more prominently, since this is a press release. PR puffery would call for a headline more like "We cured COVID and now we're going to cure Flu and AIDS (and another thing you've never heard of)."

Props for modesty, I guess, but this is a weird instance to suddenly get coy.

Bunch of reasons. The biggest (IMO) is that HIV is an STD. The next is that it is associated with the gay community.

Those two factors mean that it is nearly guaranteed to upset a bunch of religious nutjobs.

The list of things they work working on is too long for a headline. I personally find HIV the least interesting (since I'm at extremely low risk by lifestyle - I'd still get the vaccine it work works, but it isn't a big deal to me). To me the correct headline is "moderna isn't working on vaccines for any of the cancers my family members are currently fighting" I have no doubt that someone else will read the article and respond "you idiot, they work working on X which is the most important things possible" - X of course being different for each personal situation.

HIV has effective prevention through both condom use and pre-exposure prophylactic treatment. The vaccine is a big deal in reducing costs, but, it's not as big a deal as the flu vaccine (or even as big as HPV was).

Heh, I do the same for sites that have overrly aggresive GDPR-wall. Headline and comments are usually enough.

If only there were some sort of... article you could read to find out about Moderna's vaccine plans :-P

"The development programs announced today are mRNA vaccine candidates against seasonal flu, HIV and the Nipah virus."

The 1910 Manchurian plague outbreak was spread pneumonically, with a nearly 100% mortality rate.

It spread pretty well. It doesn't kill you instantly, so you can walk around and spread it before you inevitably die.


It also matters how long it takes to kill - but yes. Assume it takes a month to a kill a person... that’s a lot of time to infect others, especially if say 10 days of that are asymptomatic.

Yes. See also: ebola. If a disease is fatal too fast, it cannot spread well.

Also, Ebola spreads through direct contact with bodily fluids of an infected person, which has better mitigations than a lot of infections.

If bats are a natural biological reservoir then no. Because if the disease is less lethal in bats that's how it will maintain itself.

Long incubation period with up to 6-21 days.

The coronavirus alreay spreads before showing symptoms.

> One of these is for the little known Nipah virus.

I just submitted about this:

* https://www.bbc.com/future/article/20210106-nipah-virus-how-...

* https://news.ycombinator.com/item?id=25741798

I’d be a bit careful with those numbers. Who knows how many people really had it. Maybe a good number of cases showed no symptoms and thus were not detected?

They made a movie about it : Virus[1] on Amazon Prime.

Unfortunately due to flashbacks, which introduce non-linearity, it may be difficult for those who are not native speakers to follow through the movie. The problem is no obvious visual highlighting indicating that a scene was a flashback (like going black and white). Otherwise a really solid watch.

[1] https://www.imdb.com/title/tt8941440/

I'd assume fowl to be much more common carriers but why are bats always the ones? Is there something glaring that I am missing?

Bats get around (they can fly!) and they're mammals, so the viruses they carry are somewhat compatible with us. Not that birds aren't also virus spreaders (West Nile, etc.).

There's much more to it, of course.


It seems we need to cull a lot of bats.

that actually makes transmission more likely. more culling means less comptition for food so more reproduction, which leads to a larger number of juvenile bats. Additionally, bats eat insects including mosquitos that cause maleria and they also pollinate fruit.

It happened so infrequently. How are they plan to test the vaccine on people?

The announcement states that only the other 2 vaccines will start Phase 1 trials in 2021, and is silent on Phase 1 trials on the Nipah vaccine. There's development work before that though: in vitro trials and trials on animal models. Depending on the outcomes, they can move to Phase 1 trials, where, just like they did for the Covid vaccine, they'll look at the safety (i.e. if there are side-effects) and the immune response (how many antibodies, and what type of T-cell and B-cell response there is). If they do that, they would be in a position to quickly proceed to Phase 2/3 trials in case there's an outbreak anywhere in the world.

Very cool! Also I’d hope to see Lyme in the mix. It’s so pervasive and creates all kinds of weird dietary and nervous system issues.

>It’s so pervasive and creates all kinds of weird dietary and nervous system issues.

I am not an expert, but I think it would be amiss to omit the Lyme disease controversy with these statements. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4477530/

Lyme disease has a simple antibiotic treatment. The Lyme serology test has high false-positive rate. There might be many people who believe they have Lyme disease therefore sadly miss out on their actual diagnosis.

>Even if CLD lacks biological legitimacy, its importance as a phenomenon can be monumental to the individual patient. This is because many if not most patients who believe they have this condition are suffering, in many cases for years. Many have undergone frustrating, expensive, and ultimately fruitless medical evaluations, and many have become quite disaffected with a medical system that has failed to provide answers, let alone relief.

>Many patients referred for Lyme disease are ultimately found to have a rheumatologic or neurologic diagnosis. Rheumatologic diagnoses commonly misdiagnosed as Lyme disease include osteoarthritis, rheumatoid arthritis, degenerative diseases of the spine, and spondyloarthropathies. Some patients are found to have neurologic diseases, including multiple sclerosis, demyelinating diseases, amyotrophic lateral sclerosis, neuropathies, and dementia. Some CLD advocates have argued that these various conditions are simply manifestations of Lyme disease, but these hypotheses are untenable.

This is incorrect. Your link is from 2016. In the last few years several studies have brought to light that persister Lyme is real and very hard to eradicate with standard antibiotics. Even the CDC is starting to change their tune as their website now mentions persister Lyme as a viable theory.

An example: https://www.jhsph.edu/news/news-releases/2019/three-antibiot...

Let's let this rest as 'controversial'. 2020: https://www.amjmed.com/article/S0002-9343(20)30011-5/fulltex...

Even people here in Australia passionately declare that they have Lyme disease (without overseas travel). Our ticks don't even carry Lyme disease...

From the study you linked, first sentence: "Five clinical trials show that prolonged antibiotic therapy has no clear and lasting benefit in relieving posttreatment Lyme disease symptoms, a condition often called “chronic Lyme disease”;1, 2, 3, 4 no evidence of active infection was found in any of these studies by culture or molecular methods."

Almost all those citations are outdated studies from almost 20 years ago and one recent from 2016 where patients _did_ improve with antibiotics according to the data but the abstract concludes they didn't. ¯\_(ツ)_/¯ If they have to ignore recent studies and go back 20 years to "prove" antibiotics don't work then what does that tell us about bias in medicine?

2018: >Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined. https://www.researchgate.net/publication/324539470_Persisten...

2019: >We collected data from an online survey of 200 of our patients, which evaluated the efficacy of dapsone (diaminodiphenyl sulfone, ie, DDS) combined with other antibiotics and agents that disrupt biofilms for the treatment of chronic Lyme disease/post-treatment Lyme disease syndrome (PTLDS). ... Conclusion DDS CT decreased eight major Lyme symptoms severity and improved treatment outcomes among patients with chronic Lyme disease/PTLDS and associated coinfections. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388746/

2020: > This study, which drew on a sample of over 3500 patients ... Approximately half (53%) of the patients in the study reported some improvement, and more than a third (35%) were “high responders” to antibiotic treatment, underscoring the value of large samples, subgroup analysis, and real-world evidence as standard components of Lyme disease treatment studies. This spectrum of improvement is consistent with reports for most pharmaceuticals due to patient treatment response variation https://www.mdpi.com/2227-9032/8/4/383

They only test for Borrelia Burgdorferi. We know there are several more out there that cause Lyme symptoms. Borrelia

japonica – Discovered 1994

andersonii – Discovered 1995

lusitaniae – Discovered 1997

bissettii – Discovered 1998

spielmanii – Discovered 2006

californiensis – Discovered 2007

mayonii – Discovered 2016

I'm betting we can add the Australian variant to that list in the future.

If you’re not an expert why would you link a manuscript to stir up a thread?

CLD is real and even if it’s over diagnosed, it still doesn’t take away the many real diagnoses that exist and a vaccine would eliminate its potential permanently.

If you are posting in good faith...more recent studies are centered around making the findings in the European strain viable in the American one.

>If you’re not an expert why would you link a manuscript to stir up a thread?

>CLD is real

Well, I believe the right thing to do is to at least mention that these are controversial statements.

This misses that many many people get Lyme disease without knowing it (asymptomatic), particularly children, and if treatment it not given early in infection, permanent neurological damage occurs.

This is common in north eastern state rural areas and has been getting steadily worse.

We are constantly doing tick checks on the kids after one of our friends related that she suffered lifelong issues after being bitten by a tick 40 years ago in our neighborhood.

A vaccine would be a huge relief.

And in turn this misses that chronic lyme has become a catch-all self diagnosis people have for chronic medical problems with no clear cause. There is not really much evidence to believe it is a real thing.

To clarify, you're saying we don't know whether Lyme disease is real?

Lyme disease is different from chronic lyme disease. The latter has little evidence.

I still think it’s worth. The amount of life lost to people with chronic Lyme is significant, even if the number of infected is low.

But as the parent explained, many of these chronic Lyme patients may be just misdiagnosed. They believe they have Lyme, but the problem is some other disease.

If chronic Lyme illness is caused by lingering bacteria hidding in the body's tissues, the real way to eliminate any doubts about alternate causes is precisely to get a Lyme vaccine. Then, if the symptoms persist, we could easily deduce that the cause is other.

Except that one thing... the chronic Lyme could very well caused by an autoimmune side-effect (this is among the most serious explanations), in which case I don't think the vaccine would help.

I don't think that's a very scientific approach as a vaccine may have other effects on the symptoms.

Finding lingering bacteria would be the right call. Autopsy or biopsy. And then get better testing, less "false positive".

With no specific (set of) symptoms, symptom based evidence seems inherently weak.

Bacteria is latent. CFS is not not strep throat. Generally body-wide immune dysfunction is present.


Yes, but we're interested in the _causal relationship aren't we?

I don't see how the linked article contributes to your argument.

Tho, it's an interesting read and a warning to those supplementing vitamin D like it's the solution to everything.

This potential role of vitamin D is very exciting!

I don't know if you can read the article apart from the abstract, so just in case:

It proposes the idea for the mechanism of vitamin D supplementation to better certain conditions in the short term, but worsen health long term, by acting as a immune suppressant similar to other steroids.

Here are some excerpts:

> "Consequently, if patients with autoimmune disease succeed in killing bacteria associated with their disease state, their symptoms should be expected to escalate, at least in the short-term, as cytokines and endotoxins are generated[28]. Conversely, in cases in which the immune response has been suppressed by supplementation with an immunosuppressant such as the secosteroid 25-D, one would expect to see fewer clinical manifestations of disease in the short-term, yet more advanced disease in the long-term. At a certain point, depending on the clinical symptom or physiological markers of disease, patients supplementing with vitamin D would be expected to approach a "crossover point" when additional reduction of the immune response is eclipsed by the advancing disease (Figure 2). This outcome has been demonstrated in longitudinal studies, with studies on sicker or older patients taking less time to realize the effect."

> "The Iowa Women's Health study showed vitamin D intake seemed to protect against breast cancer in the first five years after it was taken. However, the effect began to reverse between years five and ten and was completely lost after year ten, trending towards an opposing effect[29]. Lappe et al published work, conducted over four years, that seemingly showed vitamin D might lower the incidence of colorectal cancer[30]. In a similar study looking at a larger cohort and over a longer period of time, Rossouw et al found no such effect[31]."

Why can't we have nice things, eh?!

Since, vitamin D is frequently advertised as the cure all supplement, I also want to mention "antagonistic pleiotropy" as something to keep in mind, as conceptual "immunization":


Edit: OMG. I just realized, it may very well be possible that winter's VD deficiency may be needed for good health to some extent, if the body is indeed more active against lingering pathogens. This may also explain the COVID19 and VD connection, as steroids have been shown beneficial as well, maybe it's the immune suppressant quality of VD, which turns out beneficial!

Thanks, but I read the article, and my enthusiasm is justified.

Because thus vitamin D would be a great solution against autoimmune diseases, among which are a lot of the cases under the umbrella Chronic Lyme Disease (it is supposed that the borreliosis can provoke an autoimmune dysfunction that continues beyond the disappearance of the bacteria).

A lot of cases of chronic fatigue would be treated by vitamin D, which is a huge news.

But they argue, it will make things worse and promote bacterial spread and growth...

They say the VD supplementation is comparable to steroid treatment. I don't see what's to be enthusiastic about, tbh.

In the case where there are still Borrelia bacteria you're true, but if it can be checked that the intruders have vanished (which is the case in most cases of difficult to treat CLD or CF) then it should not pose any problem.

In the case where the Borrelia are just hiding and in a latent state, then all is a question of comparating the dynamics of the two sides: the time required by the Borrelia to wake up and proliferate, vs the time required by the vitamin D to reduce the autoimmunity to the point where the body is again desensitized about itself.

A short treatment of vitamin D would be sufficient to cure the immune problem and not long enough to allow the bacteria to take over. (Hypothetically. This is just a possibility and has to be researched, but this is exactly why I am enthusiastic.)

Also, contrary to steroidal treatment, vitamin D bolsters a part of the immunity (lymphocytes T), even if it dampens an other part. So, it would restore a balance which is lost in case of defective aquiered immunity.

There is no way to eliminate these doubts. If you made a magical cure that totally eliminated the bacteria that causes Lyme disease, then these patients would take it, and it would almost certainly not work (because "chronic Lyme" isn't a real syndrome, and these patients don't have this bacteria). However, that would not convince them, they'd just claim that the medical establishment has failed them yet again (or worse: they become anti-vaxxers). You can't treat fictitious diseases with real drugs.

People are not making up illness for the fun of it. Their ailments are very real and they have a cause.

Malingering exists, but the profile of the chronic Lyme patients you speak about is not at all the one of persons in need of being nursed by the society like babies...

Just imagine you go to the doctor and all you say is dismissed because he thinks you make it up? What a despair you would be in! Speaking of a closed logical system your physician would be in! The same kind as the ones making famous conspiracy theories.

"I had <insert illness> and I was not taken seriously for <X> years" is such a recurrent theme that it is very concerning.

Just recently, the "long covid" was very much mocked by smug doctors. Imagine the distress of the patients.

You're wrong, these patients just failback on Lyme as a default and would be very pleased to discover the real causes of their ailments if it was found. To suppose that people are that much irrational and to generalize to this extent is... sorry but I am shocked.

In medicine, a golden rule is always assume your patient is honest in describing his problems.

Finally, contrary to what you said, the problem is not outside of the real world. Just as a link was proved between some tickborne pathogens and red meat allergy, you cannot exclude that one day a scientific team would prove that under some conditions the borreliosis provokes an autoimmune illness. And such a study would most likely point towards chemical markers to look for in blood and, at last, be able to diagnose it with certitude.

> People are not making up illness for the fun of it. Their ailments are very real and they have a cause.

I have absolutely no doubt that their problems are real. I fully believe that these patients are honest and that they really suffer, and they need treatment. I do not believe at all that they are "making it up".

But they don't suffer from "chronic Lyme".

There's just no evidence that it's a real thing. But just like with electromagnetic hypersensitivity, Morgellon's disease, "Wind Turbine syndrome", or any of a legion of "diseases" from medical history, you can't treat them medically if there's no evidence they exist. It would be malpractice for doctors to prescribe real drugs for fictitious syndromes, and it wouldn't do anything to convince their patients either.

Sorry if I was a wee bit harsh in my comment.

If these patients get a diagnostic, even if it is not Lyme, I am sure that would help them very much.

It is true that the medicine is more than often not yet capable of giving satisfying diagnostics, and that misdiagnostic is counterproductive...

However I remember I saw some sound studies on biofilm protein immunity that was triggering autoimmune disorder, in relation to the borreliosis. This is why I had this strong opinion. I will report here if I manage to retrieve the exact reference.

We already have a Lyme disease vaccine. However, the manufacturer refuses to sell it for human use due to PR threats from conspiracy theorists. Unfortunately, creating vaccines is only half the battle.


I found that article very interesting, and think describing the pushback as PR threats from conspiracy theorists oversimplifies just a bit.

Aa mentioned in the article, it's very possible the vaccine triggers a rare, genetically associated autoimmune disorder normally caused by Lyme disease. It was also released roughly concurrently with at least one vaccine that was legitimately withdrawn for safety reasons.

Compared to, say, the covid-19 vaccines, or the MMR vaccines, I find the public hesitation more understandable. It's not like a disease with an especially high mortality rate or one that's spread person to person.

Not saying the push to shame it out of existence was right, since it sounds like the benefits outweighed the risks at least for some people, but there's a lot to unpack. Definitely worth a read.

The argument I've always read is that it should be made available to people who live in areas with lots of ticks, not that it should be pushed on everyone.

Yes, kind of like how you should get shots for yellow fever or tropical diseases when going on some trips.

But if you begin saying you need shots to go in Poland, it's maybe not going to be accepted as easily as for tropical countries...

BTW the side effects of the shots we give to go to French Guyane is something to behold. Roommate was literally covered with red dots and it itched like hell.

Autoimmunity is so scary. It sucks that pathogens evolve to hide by exploiting the body's friendly fire avoidance.

Btw. the molecular mimicry of the spike protein may cause autoimmunity as well. Time will tell if that only applies to SARS2 or the vaccine as well.

No source: There was a paper on a model for cross reacting to normal cell proteins in /r/COVID19, but I am on mobile and blocked reddit everywhere now. Should be easy to find.

Some serious theories to explain chronic Lyme precisely suggest that it is an autoimmune reaction caused by the bacteria biofilm proteins. That would explain both why the chronic Lyme can persist even after the bacteria have seemingly been eradicated, and the effects of the vaccine sometimes observed.

In this case the vaccine's purpose is defeated, as the real life-spoiler is the chronic Lyme. Acute Lyme is well treated by the antibiotics.

This is misrepresenting the real limitation of the vaccine that dampened demand...

> First, the vaccine efficacy of <80% meant that 20% of fully vaccinated individuals could still get Lyme disease [20]. Second, achieving full protection required three vaccine doses given at the time of the initial dose and 1 month and 12 months after the initial dose. Third, the vaccine safety and efficacy database lacked tests in young children, a population at high risk of developing Lyme disease [3]. Also the vaccine was effective only against the predominant North American Borrelia strain without necessarily conferring protection against international subspecies [16, 22]. Finally, uncertainty about the length of vaccine-induced immunity implied that recipients might need booster vaccine doses as often as every year to prevent waning immunity.

The real underlying malicious behavior here was from the lawyers who actively recruited and fomented anti-vax culture...

> The final agreement included over 1 million dollars in legal fees for the prosecuting lawyers, but provided no financial compensation to the ‘vaccine victims’.

Isn't that exactly what the National Vaccine Injury Compensation Program is supposed to prevent, by isolating vaccine makers from liability in exchange for a 75-cent tax that funds a no-fault compensation program?

I expect that the fear here would be that it'd be a PR disaster for the manufacturer, not a legal/financial one.

It's very odd that dogs can get vaccinated for Lyme but not humans...

We can also have dogs "put to sleep" but not people. You can also keep a dog on a leash. If a dog dies, there's no need for a coroner's report. It's not _that_ odd that human and dog medicine are held to different levels of testing and safety.

> We can also have dogs "put to sleep" but not people.

It's not like this is without controversy; it's an active political battle.

I think this was rather implying we put down dogs, if they break too expensive to fix. The vaccine was probably grinding through loads of "pets" in development.

Very different than "putting down" terminally ill people on their own choice and action.

Tho, maybe similar to the eugenic endeavors of the past. I hope you're not implying that's what's in debate again.

> We can also have dogs "put to sleep" but not people.

Depending on where you live, you can have humans "put to sleep" as well.

It is legal in 9 US states, Canada, parts of Australlia, and probably otherplaces as well.

> You can also keep a dog on a leash.

Some people keep their children on a leash as well.

I think in most of those places you have to ask the human first.

No, people just put their kids on leashes in public. It’s... well, wild but the opposite.


I wonder about the trolley problem that is medical testing requirements.

It seems like we, as a society, would tend to never want to pull the lever to save more at the cost of risking a few. Social and contractual liability makes it a bad trade.

Acceptable risk is very low which can, paradoxically, cause more death and discomfort.

It would be nice to see a greater awareness of the tradeoffs. These things tend to get emotional, though, so not much gets done.


You can't make trolley problem tradeoffs when there's enough uncertainty involved in all the steps.

Older medicine is filled with supposed cures to issues that cause issues down the road. We also have countless medical trials that show no positive effects on the disease it's trying to cure, and outright ill effects (both short term and long term).

If we _did_ have visibility and a good understanding of the effects of stuff, you would think that Covid, of all things, would push at least some people more down this argument you are making.

But basically everyone involved (including many many people who had extreme incentives to push a vaccine through) stuck to the trial discussions.

I do understand the "Extenuating circumstances" argument. But this sort of massive generality reeks of Dunning-Krueger.

A problem is it's not really the trolly problem because the punishments if things go wrong accrue to different people than the rewards if they go right.

Theoretical question here: Do you want to be the one sacrificial lamb that dies, in order for the rest of us to live?

If you want to play Jesus here, then I’m sure the rest of society will support you.

It isn't that stark though. There are current policy choices that result in statistical deaths. Other policy choices are quite likely to result in fewer statistical deaths, but you've somehow decided that the current policy is not even up for discussion.

Pets are considered property in all fifty states (Although in CA there are laws being proposed or even passed to change some of that). Any injuries or death to a pet only requires replacement cost.

You can orally actually vaccinate the reservoir species (mice) in targeted areas as well to disrupt the enzootic cycle.

We've also have coronavirus vaccines for dogs for a long time. More tolerance for side effects means easier approval means more vaccines which haven't been proven safe to the standards we demand for use in humans.

biontech also just published a paper on how they're trying to tackle MS. mrna therapeutics are exciting stuff!

I saw this right before I came here: "FANTASTIC NEWS—A potential vaccine for multiple sclerosis is now within sight on the horizon! And it’s an mRNA vaccine by BioNTech, maker of the Pfizer #COVID19 vaccine. Study in mice shows great promise for improving symptoms & stopping MS progression!"


The HIV one is interesting, I wonder what strategy they will use with that?

Some more detail in this article from July, they’re using mRNA to make the body produce virus like particles


Any effective HIV vaccine would presumably cause false-positives to the HIV antibody tests. Recently an Australian COVID-19 vaccine candidate trial was halted due to participants developing antibodies to proteins in the vaccine that were taken from HIV genome, causing false-positive on a HIV test. [1] Such false-positives could easily be co-opted by anti-vaxxers especially in light of the the famous Soviet Union disinformation campaign "Operation INFEKTION" [2] that falsely suggested the HIV/AIDS is a man-made virus created by the United States to cause genocide of Africans. In rural Pakistan, health workers have been killed by villages who see the polio vaccine as a Western conspiracy to sterilize Muslims.

Global mandatory inoculations using a safe and effective HIV vaccine that causes false-positive results on HIV antibody tests would be a field day for anti-vaxxers and conspiracy theorists everywhere.

[1] https://www.livescience.com/australia-covid-19-vaccine-false...

[2] https://en.wikipedia.org/wiki/Operation_INFEKTION

Taking into account anything conspiracy nutjobs have to say about this stuff is an exercise in futility. They will not not find another wild excuse to declare conspiracy.

That might be the case, but it was just another way of saying that causing false positives on HIV tests is a huge issue for a vaccine. It should absolutely be prevented if possible, or at the very least adresssed somehow.

If the vaccine proves effective, you could do a test before and then vaccinate on negative knowing you test positive afterwards for a while.

It's very different to a false positive to _another pathogen. That leaves you blind, indeed.

Well new tests have to be developed, that don't trigger when people are vaccinated but non ill.

In Spain we had a snow storm and we have now people calling it an hoax and saying that it was not snow but plastic sent by the government.

What I mean by that anecdote is that conspiracy theorist don't need anything special for creating their theories, they cannot be the ones leading the agenda. Work on explaining why and how these vaccines work / create FPs is the way to go.

> Global mandatory inoculations using a safe and effective HIV vaccine that causes false-positive results on HIV tests would be a field day for anti-vaxxers and conspiracy theorists everywhere.

There's no reason for it to be mandatory. It's not like COVID19 or the flu where it is often transmitted through casual contact. There is simply no reason to delay/halt an HIV vaccine for just causing an false positive on a test. As you said, any effective HIV vaccine will likely have this issue so pushing forward is the only option.

Definitely. I'm sure the then-flawed antibody tests would be retired and replaced with PCR tests.

"PCR" doesn't mean "more precise". It's limited to viral DNA/RNA presented. I don't think there is much HIV circulating, if you're not sero-converting. HIV isn't shedding constantly.

E.g. SARS2 PCR will often fail for blood samples.

I think you’re misunderstanding the problem. We already have vaccines that cause positives on antibody tests. This is quite common. For example, the HepB vaccine causes positives on the HBsAb test, and people who administer the test understand this.

If we had a widely available vaccine and effective vaccine for HIV that affected certain tests, this would easily be justified by the benefit of the vaccine in preventing HIV. And the results of the antibody tests could potentially still be used to assess HIV immunity.

But a COVID vaccine that caused HIV tests to report positive without conferring any immunity would be bad — the test would essentially become useless. Re-engineering the vaccine to avoid this seems like a no-brainer.

I mean, the mRNA vaccine would work by producing specific parts of the virus so as to allow the body to mount an immune response, just like the Covid version does... So yes, you would expect HIV antibodies to be produced.

Personally, I think most people care more about having vaccines for diseases like HIV than worrying about what anti-vaxxers and conspiracy theorists believe.

Wouldnt you want a hiv vaccine to create hiv antibodies? What other mechanism is there for the body to fight off a virus?

I believe the other kind of specific immunity mechanism is referred to as "cellular immunity". But yeah, I had the same thought you had.

It's also very different if you shade the target disease tests, or of an unrelated pathogen. You'd only need to test positive before to rule out infection. It's not like your HIV status is known to anyone else, so it's a matter of information management, not risk inherently.

If we get an HIV vaccine it may also be therapeutic for HIV+ people. So far vaccine development wasn't getting anywhere because we're at loss with the nature of the virus. _If we find a persistent target, HIV may burn out in those infected and vaccinated. Seroconversion may then be something to look forward to.

This shitty mobile client can't do edits... Of course I mean test negative to rule out infection.

And could you blame people for being paranoid when the CIA have used vaccine programs for various purposes in the past.

Though they've apparently now stopped.

I assume you are referring to the time the CIA co-opted an immunisation programme as part of the hunt for Bin Laden.

I don't think anyone has ever seriously suggested that the CIA has tampered with the vaccines. They merely co-opted the inoculation process in order to gain a biological sample.

I'm not suggesting they have, but it will make people in these rural communities rather paranoid or impressionable.

> I don't think anyone has ever seriously suggested that the CIA has tampered with the vaccines. They merely co-opted the inoculation process in order to gain a biological sample.

Its not about CIA tampering with the vaccines. The assumption was that the vaccination programs were politically neutral, a system meant to better humanity regardless of politics or military targets etc etc and in many places, that's what was said to convince people on the ground.

Unfortunately, the use of a doctor to aid in information gathering for the CIA in a vaccination campaign means that that assumption is completely gone.

The context is that the Pakistan and Afghanistan border region is the only place in the world where polio still spreads, while the rest of the world it has been eradicated.

However, there is already suspicion due to lack of education and literacy that the vaccine is some sort of Western plot. So all this did was ensure that there continue to be attacks on polio and other vaccination workers in the area by 1. terrorist groups which was happening anyway, but 2. by uneducated paranoid people who think that the vaccine has been the "plot" of the western governments to do something bad to them.

All in all, the CIAs use of a charity organisation and a vaccination drive as a front for its activities has basically led to hundreds being affected by polio, unable to live their lives in good health or even in death.

It doesn't matter whether they tampered with the vaccine. They destroyed trust in international vaccine Programs and the Health Workers that are administering the vaccines are facing the blowback.

I wasn’t defending them, it was a terrible idea and the cost immeasurably outweighed the benefit of killing an, admittedly, horrific human being.

> Such false-positives could easily be co-opted by anti-vaxxers

I'm less interested in how anti-vaxxers think, than the fact that the HIV test will need to re-target a different protein.

Damn can you imagine? I never imagined that an HIV vaccine would be possible within my lifetime. Kind of reminds me of HepC. An older coworker told me how a friend killed himself back in the day for getting HepC from tainted blood (pretty much a death sentence at that time and it consumed him). But now it’s possible to CURE it and hopefully it’ll be the same for HIV soon. Fuck, science like this is amazing.

Just to be clear, a vaccine doesn't cure a disease. It prevents one from contracting it.

Also worth mentioning that while we don't have an exact "cure" for HIV, we do now have treatments that (if you or your country can and will pay for it) can make having HIV into something that not only doesn't ruin your live, but that even can't be spread from you to people you have sex with.

Getting to the parent comment though it's amazing how far we've come in that we already do have virtually 100% affective prevention from medicine. PrEP and the knowledge that non-detectible = non-transmissible.

I've been re-watching Queer as Folk which isn't that old and it's crazy how aged it feels because we've made so much progress over the last 10 years. BTW amazing show if anyone hasn't seen - wish you could get HD version with the original soundtrack.

QAF (US) was amazing - got them on DVD, and was the only way I could watch them ~ 15 years ago.

For what its worth, PrEP is not without its own costs. Besides the documented side effects, it also seems to rapidly accelerate cellular aging.

I have the DVDs too. It's worth the lower quality just for the music. Some of the most powerful scenes are deeply tied to the nusic for me, dancing at prom, Brian's bowling, the first episode, so many more - the replacement 'music' they hacked together is horrible too...

Wow i didn't know the cellular aging part thank you. Do you have anymore info? I'm on it (or was when I could actually be around humans ;( )

The biggest downside I know about is the cost. It's insane even though i have really great insurance. Gilead does reimburse but it takes like 6 weeks or more. A low income person can't be out almost 2k for that long. Medicade/care is also a pain especially those most at risk, IV users, etc. Hopefully I've heard it goes generic soon.

I feel like we are 5-15 years away from being able to eradicate or relegate sadly to the developing world only.

The music on the show deeply influenced my musical tastes for at least a decade. The most moving scene for me personally was Brian bicycling by himself (S04E14) - for the longest time I would get weepy just thinking about it, and how it seemed to reflect where my own life was at the time. The music really tied it together - Wonderful Life by Colin Vearncombe.

The cellular aging - it's something I discovered recently myself, when it was mentioned in passing during a talk on aging. I did some reading and I think this is it:

* [Brief Report: Differential Effects of Tenofovir, Abacavir, E... : JAIDS Journal of Acquired Immune Deficiency Syndromes](https://journals.lww.com/jaids/Fulltext/2017/01010/Brief_Rep...)

* [Tenofovir disoproxil fumarate induces peripheral neuropathy and alters inflammation and mitochondrial biogenesis in the brains of mice | Scientific Reports](https://www.nature.com/articles/s41598-019-53466-x#Sec24)

* [Pharmacogenetic Analysis of the Model‐Based Pharmacokinetics of Five Anti‐HIV Drugs: How Does This Influence the Effect of Aging? - Chen - 2018 - Clinical and Translational Science - Wiley Online Library](https://ascpt.onlinelibrary.wiley.com/doi/full/10.1111/cts.1...)

Accelerated cellular aging has been noticed in HIV+ patients for a while, and there is some growing evidence that at least some of it might be due to ART, including the formulations used in PrEP. I'm not aware of a study looking at accelerated aging in HIV -ve people using PrEP.

I suppose the risks are elevated with the daily dose regimen, and Event Driven PrEP (2+1+1) might be safer long term. Of course, Event Driven PrEP recommendations also assume fewer than two sexual encounters per week, so it's not for the more 'social' amongst us.

I'm unfamiliar with the pricing. How much is the out of pocket costs? Does Gilead reimburse the entire copay?


HN is amazing sometimes ;)

I was 17/18 just becoming independent in college when I discovered the show and it gave me so much confidence.

'No excuses. No apologies. No Regrets", "F*ck em all", or Justin's self actualizing speech to his therapist and mom that I won't repeat here lol.

Yeah Gilead will reimburse all the copay. I guess so they can charge insurance/government an insane amount. Which is passed along to us anyways...

I think it was like $2000 out of pocket for me for 3 month supply. and i have really really good insurance.

Yeah the one dating experience i have had in covid that actually progressed I used that short time frame dosing.

Though in normal times for most PrEP users it would seem impossible to schedule sex in advanced or too frequent to do that.

But still really good research on how effective these drugs are. maybe we'll get more research into short term PeP - though i think that's a different drug combo.

Any idea if Descovy is similarly reimbursed by Gilead?

That's what I'm curious about too (just an engineer with no medical degree). There are a lot of viruses that are simply undetectable by our immune system so it never triggers a response (similar to cancer). A good example is the herpes family. I was under the impression that you can't fully cure herpes because it hides in your nerve cells. I wonder if mRNA can force an immune response to cure this.

Some vaccines are also cures.

In the case of HIV, the problem is not that the body is unable to properly respond to the disease, the initial infection is usually benign and the immune system produce the antibodies necessary to fight it, that's what being HIV+ means.

Problem is, HIV mutates so quickly that the immune system is essentially playing whack-a-mole and cannot eradicate the virus completely.

A vaccine that imitates a real infection perfectly is mostly useless, because it will train the immune system on the wrong mutation.

The trick here is to focus the immune response on parts of the virus that don't change, by using mRNA that only produce these parts.

It is like telling the body what the weak point of the virus is. It is useful both before and during the attack.

HIV does not mutate in the body. Viruses mutate over tens of thousands or millions of patients. It does not evolve within the space of a single person's infection and does not use mutation to evade the immune system.

Here's an article about HIV mutating in the body: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4574155/

Influenza can barely even copy itself accurately.

Here's an old article highlighting escape mutations evolving within the span of a single person's infection.

* [HIV evolution: CTL escape mutation and reversion after transmission - PubMed](https://pubmed.ncbi.nlm.nih.gov/14770175/)

In case of HIV, though, it may also (partially) replace medication, considering that the virus is hiding from the immune system for a while.

Sorry if this is a stupid question, and I'm sure this is very positive news. But one question I didn't find an answer to in the press release: what's the value of using mRNA for flu vaccine? Will it result in a safer or more effective vaccine? Be cheaper and easier to produce? Something else?

I (mostly) understand the mRNA process, just curious about why it'd be superior.

Safer, yes. (No interaction with the nucleus, very simple and straightforward conceptually, plus a few engineering tricks to make it amazingly effective: https://berthub.eu/articles/posts/reverse-engineering-source... )

Cheaper, well, it depends. (Vaccines are already cheap, especially because they are mass produced.)

But I'm guessing - but I'm a total layman - that Moderna is betting big on their mRNA platform. The "beauty" of it is that you really need to just copy-paste some part of the virus (pick protein from the viral genome), and literally just paste it into their vaccine deliver platform. (See the link.) And this means R&D costs could go waaaaay down.

Sure, clinical trials are still needed to make sure it's safe and effective, but now they have a very good choice of nailing it on the first try, every try. (Basically unless they pick a wrong protein, it will work "every time". And it's already possible to get antibodies from folks who have "seroconverted" - that is they have become immune to something, because they have the antibodies against that thing. So, they sample a lot of people, look at what the human immune system did, and just pick the most common/stable protein target.)

The flu virus is problematic because it evolves/mutates fast, so old antibodies might not fit the new proteins. Yeah, sounds crazy, but some (!) small mutations lead to still functioning but sufficiently different proteins. (Of course we don't really see all the mutations that led to non-functioning proteins.)

It's also possible - super total speculation here - that the scientists/professionals/experts have a better guess on what to target than our immune system. (Relevant buzzwords: immunodominant / conserved epitope; epitope is the part of the target protein that the antibody/T-cell/B-cell actually matches/binds-to , and if the virus changes that part, boom, new virus, "doesn't look like anything to me", for example in case of HIV: https://pubmed.ncbi.nlm.nih.gov/21115730/ )

Not a stupid question

You don't have to mess around with proteins.

Producing a new protein and especially purifying it is a ton of work. mRNA is comparatively simple to produce

From what I understand, it gives more control over the immune trigger. Perhaps it's possible to sequence a small part that's common to many flu viruses and administer that?

Well, most flu vaccines today are made by infecting fertilized eggs, so an mRNA vaccine would have the advantage of being vegan. It may eventually become cheaper to manufacture.

Uninformed speculation: I would hypothesize the mRNA process could react faster to flu mutations, the current vaccines are kind of trying to guess which strains are going to be important in the next flu season. It is also possible the mRNA technology could cover a broader spectrum of flu antigens.

Influenza genetics are weird: https://www.cdc.gov/flu/about/viruses/change.htm



Clearly Flu, HIV, and Nipah are more pressing, but I found myself wondering last night what the odds are of a rhinovirus vaccine being in the cards thanks to rapid progress SARS-CoV-2 has pressed us to make w.r.t. RNA and protein-like vaccines.

Economics is the largest barrier in my mind. While my understanding is that these vaccines are less expensive to produce, it's hard to convince people to get the flu shot, let alone a common cold shot. What's more is that with hundreds of variants, it's efficacy would be hard to get right.

That said, I'd gladly pay a heft amount yearly if it meant I had a >60% chance of not catching a cold that year.

Would it be easier to cover more flu strains with an mRNA vaccine? Could we shove like 100 in there?

There is a Netflix documentary called Pandemic about couple that is trying to eradicate flu. They found vaccine that works on all flu viruses but it takes 6 shots to work. That’s not practical at all therefore it’s not on the market yet.

I have a debilitating fear of the flu and would ABSOLUTELY be up for a 6-shot regimen, if it gives me my winters back.

Seriously? Debilitating? Curious why?

I now have the same for covid, lol - but I'm overweight and 41, high risk as a result, and have two kids under 4 I'd like to see make it to graduation.

I have a constant nasal drip, that I don't think is flu related, I get the vaccine every year, but I do get bronchitis like every other year and it wipes me out for at least 2-4 weeks.

I'd totally take that, assuming reasonable convenience and cost.

6 shots is not that bad. Many people get a shot every year, so as long as it protects you for 6+ years, it's better than the alternative.

Interesting. What are the required timing of the six shots, the percentage effectiveness, and the duration of protection?

I dunno, plenty of people take an annual flu shot already.

Conspiracy glasses on, what if the annual flu vaccine manufacturers are actively preventing a universal vaccine from happening? It's a big recurring source of income for them after all.

Big reward for any defector and that it is hard is a pretty good explanation for not having one yet.

There are a number of weird diseases that some suspect are side effects of flu infections. It may be that we have to prove a causal link to one or more of those before an elaborate flu vaccine is seen as worth the trouble.

There is very little scrutiny of people who have initial mild flu or no long term respiratory complications. Perhaps more light will be shed in the wake of the over zealous scrutiny that comes with covid 19

There’s a (non-mRNA afaik) universal flu vaccine by the NIH in phase 1 since April 2019: https://www.nih.gov/news-events/news-releases/nih-begins-fir...

Not a virologist so I might butcher the explanation, but I think the strategy for universal flu is to target the “stalk” part of the virus since it’s similar across strains. We currently target the surface proteins since it’s easier to make a vaccine this way, but it differs more across the strains. Going after the stall would mean we don’t need to shove 100 different strains in there. I don’t know if this will be easier with mRNA technology.

Also, can we get a vaccine for most of the common colds??

Found this:


> Vaccines target a specific virus or pathogen. One difficulty with developing a vaccine for the common cold is there are at least 200 different viruses that can cause cold symptoms, including rhinovirus, coronavirus, adenoviruses, and parainfluenza.1

> Rhinovirus makes up about 75% of colds. Still, there are more than 150 strains of it circulating at the same time.

> At this time, there is currently no way for one vaccine to protect against all possible strains that can cause the common cold.

It also goes on to say it self-resolves and only causes mild illness.

So they potentially could find a vaccine that covers most, but I'm guessing would be a waste of resources.

I'm ignorant, but could they put a tiny dose of all 175 variants into a single shot and yeet that into people in one go?

This could be done with the mRNA technology, where you basically "print out" the requested mRNA overnight. Encoding several proteins is possible.

How the organism would react to such a flurry of foreign proteins, that is another question. 175 unknown proteins is a lot, the immune system could be roused beyond safe levels. It is possible to kill a person (or a mouse) by overstimulating its immune system.

I'm pretty sure we have way more than 175 different antigens at any given time putting our immune system to work. Or we would, if we were still living in nature. In fact, I often think the issue with Covid is more than anything else our chronically debilitated immune systems.

The question is how many are novel though, not how many there are.

This is a question that would need experiments to settle. AFAIK the original research around mRNA vaccines had to navigate the gap between "not stimulating enough" and "stimulating too much" very carefully.

Is there a medical definition for “yeet”?

Rhinoviruses make up ~75%, but the other 25% are made up of only a handful (4 iirc) of coronaviruses. Definitely seems like you could at least make a vaccine for those, and eliminating 25% of colds would be nothing to sneeze at. (Pun very much intended...)

Sure, but who do you know that’s willing to get 100 flu shots in a year?

Not sure if this is a flippant response, but I believe the parent post meant 100 strains in one injection.

You can put more than one drug in a single shot. The MMR vaccine contains Mumpsvax, Attenuvax, and Meruvax to fight the mumps, measles, and rubella, respectively

I think OP means one shot with a lot of strains in it.

I am curious how a trial for the HIV vaccine will proceed in a world where PrEP is available.

PrEP might be available, but there are still countries where it is not easily accessible, and where HIV is still spreading.


I can see it going full steam ahead, myself, for a few reasons:

1) Do both, for additional safety.

2) PrEP has changed formulations, and may change again. This implies that the previous formulations were not completely optimal.

3) From what I understand, PrEP can be expensive, although your insurance may cover it. You can also get it overseas for much less but many are not comfortable with that.

4) It's a lifetime expense, even with insurance and a lifetime of having to take a drug versus one or more shots.

5) Not having to undergo kidney function tests on the regular might be nice.

The problem with “do both”: if you give your control group PrEP, then you won’t be able to get data to support the vaccine’s efficacy. A trial requires enough infections in the control group to show the vaccine is better.

Drugs are controlled against the alternative treatment often enough. The study needs to be designed differently, but statistics can do this.

You pick a high risk group that either doesn’t have access to prep

For the HIV vaccine trials, all participants are educated about and are offered free PrEP. There will be participants who choose not to take the PrEP anyway, and there will be people who are not compliant with PrEP's dosing schedule, which will reduce its efficacy against HIV acquisition.

That's only a problem for the studies. I'm talking about after the studies. I can see a lot of at-risk people saying "Yeah, I'll do both."

I was joking to my doctor that when I get access to the COVID vaccines, I plan on Moderna in one arm and Pfizer in the other.

The comment you replied to was specifically asking how the trial would work given PrEP though.

There's a lot of places in the world that have not approved PrEP. And just like a birth control pill, it has to be taken daily -- and that is something that is hard for a lot of people to do consistently.

Even in the West, isn't it really expensive?

The sticker price is very high but nobody pays it. It’s free even if you are uninsured, and if you are insured Gilead will reimburse you for any copay.

I think the production cost is not that much, so the high price is just a means of extracting profit from the insurance programs.

Unfortunately, you have to give Gilead massive amounts of PII and paystubs/etc for the uninsured free programme, which is utterly insane to an outsider to think about.

> It does not have to be taken daily. You can take PrEP 'event driven', it is 'approved' this way by the WHO for MSM: https://www.who.int/hiv/pub/prep/211/en/

(Apparently event driven PrEP is indeed not approved or recommended for women.)

> Even in the West, isn't it really expensive?

One datapoint: In Belgium the out of pocket cost is 5 euros per package of 30 pills.

I've looked into it and they offer free PrEP to anyone in the trials that wants to take it.

There are probably a lot of people who are willing to take a one-time vaccine but not an expensive, daily series of pills which aren't completely free of side effects.

The initial trials just need to establish that the vaccine is safe (no severe side effects) which could include those on PrEP and even those with no risk factor.

The larger, latter trial that needs to study efficacy could simply use a large population. While HIV transmission is much more rare outside of certain high risk groups, infection does occur through accidents or deviations in behavior (e.g an EMT gets a needle prick while trying to administer Narcan). It would take a larger population and longer study but it should still be able to reach statistical significance.

I didn't know about PrEP, but from what I've just read it has to be taken daily in order to be effective. A vaccine could be a safer method.

It does not have to be taken daily - https://www.iwantprepnow.co.uk/how-to-take-prep/

I agree it would be better in the end after it’s approved. I’m thinking about getting the ethics board to allow a trial where you have to give half of the participants a control (and the other half a possibly-ineffective vaccine), when a known-good alternative exists.

The other reply has a solid point. Maybe you can find a country where it’s not possible to distribute daily PrEP, but is possible to vaccinate people and then test them for HIV monthly.

True. On the other hand, the effectiveness of PrEP is thought to be as low as 74% among people who inject drugs. It might still be possible to find such people for trials. We should still see a statistically significant effect even if they are taking PrEP daily.

They solved the ethics problem by offering trial participants PrEP for free for the duration of the trials.

Some people who start the trial not taking PrEP will also continue the trial without taking the PrEP they're offered and educated about for free.

Really good news!

Hopefully these get approved relatively quickly. I'm most excited about the seasonal flu vaccine. That could be a major game changer.

Yeah I agree - so much of the original downlplaying of Covid was along the lines of "Well, the flu kills 50,000 people per year and we don't take extraordinary measures" which is an insane line of thought for multiple reasons but not least because we just write off 50,000+ people per year without much of a stink.

Now its moved to “but lockdowns have been going on so long that this is just normal deaths from everything else” and “thats not a covid death!” Not realizing that the flu also has those same counting errors or overlapping causes, leading everyone to begin clarifying “complications related to COVID-19”

“Fortunately” we get to see how much further their mental gymnastics will go as the death count will begin greatly exceeding all other causes over the next 3 months!

Any guesses?

“It was a tough winter for people that already were stressed!”

yeah, I've already started hearing the "but all the side effects from the lockdown are worse". Which of course dismisses all the non-death side-effects from covid.

Don't they already have flu vaccines. I thought the issue was that they changed so rapidly the vaccines can't keep up?

Yeah, it's very difficult to predict which are going to be the dominant strains so they take a best guess, include the several candidates that they expect to be most virulent that season and ship that as the "flu vaccine" that season.

The hope is that with a much faster time from approval -> production, in theory we could reassess in October / December / February and vaccinate against the most virulent strains that are actually showing up in populations. There are reports that Moderna had a vaccine developed in two days once they received the sequence from researchers. If they or similar companies received "platform" approval to ship new vaccines with abbreviated testing, it could dramatically change how we vaccinate for the flu.

Specifically we guess based on the other hemisphere since flu is mostly a winter illness -- People report "flu" year round, but the deadly Influenza virus is most "flu" in winter, whereas in summer most "flu" was just a bad cold, in medicine the term is ILI (Influenza Like Illness). This gives us several months between the worst of their Influenza cases on the far side of the world and us needing to inject our vulnerable populations with a vaccine.

This means the relatively mild flu load in Australia and especially New Zealand actually hurt this year's Northern Hemisphere guess - they were isolating because of COVID-19 and so they had far fewer than usual cases on which to base guesses.

That would be an amazing world. What do regulators think of the "platform approval" concept, though? I can't imagine that this kind of approval currently exists under most governments' regulatory regimes for vaccines.

I think over the next 10 years governments, scientists, and businesses are going to be asking themselves how they can be prepared for the next pandemic. This will make governments more likely to approve a fast track for the mRNA platform, and popular support more likely to sway in favor of this.

If we had generic facilities that could produce any mRNA vaccines, and an mRNA vaccine approval process that takes 30 days then we could have had covid vaccines ready to go before March 2020, and those whole story looks very different.

My understanding is that this, or something like it, is already done for flu vaccines; that's exactly how they're able to release updated versions each year.

I'm thinking down the line they could put more than the 3-4 strains in the vaccine that are in the current ones (Moderna is aiming for four right now, which is what the other "industry leaders" do). But I am not an expert, at all.

I think the idea is the mRNA vaccines are much faster to produce which makes it easier to keep up (but I could be wrong, this isn't my area of expertise).

I can't understand people who wants to get vaccinated yearly for just a flu. Please make me understand. I mean it's just a flu and we have Netflix.

As a Moderna shareholder I think that is stupid. As a healthy eater I think that is really stupid. Now I can only think I must be really stupid.

I rarely get true flu, but when I do, every 15 years or so, I definitely cannot just lie around and watch Netfix. It is excruciating.

You've probably never had the flu, you've had a cold you called the flu. A week of not sleeping because you're alternating between burning up and freezing, diarrhea and aching muscles is not pleasant.

Because it's really simple to do? It sucks to be sick, and there's a usually free, probably effective means of avoiding it. Plus, if you're around people for whom it's not "just" the flu it helps protect them.

Surely you've heard the arguments against people making this same case for COVID. "I'm young, so it's not going to kill me - what's the big deal?" First of all, even if it's unlikely, it could kill or debilitate you. (Both covid-19 and, to a lesser but still present extent, the flu.) More importantly, if you don't get it, you can't pass it on to someone else who might be at higher risk.

And on top of those excellent reasons, getting a flu shot is a momentary discomfort, so why not, even if just to avoid the potential discomfort of a flu?

Same as Covid - getting a flu is a real ordeal for most people with days of fever and myalgia and if you pass it to your elderly relatives there's a chance it will kill them.

The vaccine is harmless both for you and your elderly relatives, so it is (a) smart to get it to avoid suffering yourself and (b) socially responsible to get it to lessen its spread to people it will kill.

For you it is just the flu, for others it's a death sentence.

The reason to vaccinate for the flu is to stop the spread of the flu to vulnerable populations. The cost of vaccination is a little arm soreness for a day or two (hardly anything).

The added benefit is that you've decreased your odds of being put out of commission for 7->9 days (if you are being responsible). Current flu vaccines are around 40->70% effective. Not great, but better than nothing.

The reason I'm so excited about the moderna vaccines is that it can drive those efficacy rates much higher. That's because they can delay manufacturing to be far nearer to the outbreak. The key to a highly effective flu vaccine is matching the strains. mRNA vaccination presents a way to do that a lot better because you don't need 7->10 months of lead time to make sure there is enough supply.

Why? Does elderberry not work for you?

Some anecdata: I had the flu NUMEROUS times as a child/young adult. I know what the flu feels like. A couple of years ago, I got the flu (no, I didn't go to the doctor because I knew it was 'just' the flu). I was feeling crummy one day, and the next I was curled up in bed, unable to move, fever with body aches, and slept most of that day. My wife told me about elderberry and gave me 4 or 5 spoonfuls of an elderberry tincture throughout the day. The next day, I was shoveling compost in the yard.


Above, 2004 - “These findings need to be confirmed in a larger study.”

2020 - https://pubmed.ncbi.nlm.nih.gov/32929634/

“We found no evidence that elderberry benefits the duration or severity of influenza. Post hoc analysis suggested primary outcomes with elderberry taken alone (without oseltamivir) were 2 days worse than with placebo taken alone. Our results contradict previous studies and demonstrate the need for further studies.”

We can all do our part to stop pubmed abuse.

You didn't know whether it was just the flu. You don't know what your results would be otherwise. Don't give advice based on n=1 where you don't even know the disease.

You can have flu you barely notice as well as common cold that keeps you semi-conscious for a couple of days. Unless you get swabbed, you just can't know.

It's also not uncommon to have a "24 hour flu", which aren't actually caused by flu viruses, but result in flu-like symptoms for roughly a day, then a rapid recovery. Sounds like that was the case for OP, and I doubt elderberry had anything to do with it.

And that's why noone dies from it anymore.

A few weeks ago, I looked for info on how the mRNA itself is produced/created in these vaccines, but couldn't find the answer. Does anyone know?

"Therapeutic mRNA is typically synthesized using in vitro transcription (IVT) with single-subunit polymerases (e.g., T7, T3, and SP6) using a DNA template to produce multiple copies of the coded mRNA. T7 RNA polymerase can incorporate chemically modified nucleotide triphosphates (NTP), particularly uridine modifications, which have been shown to maintain translational efficiency and alter the interactions between exogenous mRNA and TLR7, TLR8, and RIG-I (20)"

* [Impact of mRNA chemistry and manufacturing process on innate immune activation | Science Advances](https://advances.sciencemag.org/content/6/26/eaaz6893)

Didn't Moderna already announce the seasonal flu vaccine programs on the research presentation day?

Anyways, I really hope them to succeed, my mother didn't take the flu vaccine ,,because it's risky and not that useful anyways''.

Moderna can make it much more efficient with less side effects, so I'm looking forward to it.

Vaccines are interesting, but I'm much more intrigued by what this may mean for future therapeutics if their methods work well moving forward.

There are a lot of companies (including mine) that have been working on personalised, target, combinatorial, interfering, etc. RNA therapeutics for quite some time. The success of RNA vaccines in the last year has really opened up the potential for pharma partnerships to test and develop these kinds of things. They have built out the infrastructure and there's a broad confidence and awareness of the basic concepts that was previously largely missing. Pharma just really loves proteins.

The next 5 years are going to be incredibly exciting - it has the potential to fundamentally change humanity's relationship with many kinds of disease.

Can you name some of these companies or what to search form. I'm curious what things they are working on.

I thought that only Moderna and BioNTech have the licences for mRNA vaccines.

Astrazeneca is working together with Moderna on respiratory diseases, which is interesting for me, as I have asthma.

Actually vaccines can be used for lots of therapies. One example is using personalized vaccines for creating immune reaction for cancer by sequencing the cancer DNA and comparing it with non-cancerous DNA.

Sorry. Yes, this is exactly what I was referring to.

Yes, from the article you can see they have been working on this flu vaccine since 2019 - before covid. They haven't had as much money, so it takes longer.

Yeah, I guess now they can get infinite amount of money, so what matters is the amount of money they can spend efficiently.

Can someone fill me in here. I have tried my best to read, and educate myself about these mRNA vaccines. But I have yet to see any conclusive evidence or proof that having the vaccine for COVID-19 prevents you from actually getting COVID-19. And i've seen many people debating this in the comments of other HN threads. It might mean you are asymptomatic, and _less_ likely to spread your symptoms - but it still means you can theoretically harbour the virus and spread it on to others (e.g. through kissing)

So, the question is, given we already have medication which works well as treatment for those with HIV - what exactly will this vaccine do for HIV - if not stop the transmission? My understanding is HIV is primarily spread through sex and sharing of needles. A vaccination program won't stop that.

Thanks in advance. I would love to read more about this.

I'll try. I'm no expert but I read a lot about this and people keep asking me to explain it to them. First of all, there is no way to entirely prevent infections and transmission of something that replicates in poorly perfused (low blood flow in the area) upper airways. The immune system works by carrying stuff to infection sites via blood, and so you need enough blood at the place where the virus is before it can be attacked. That's why nobody is claiming total protection from infection and transmission. However, this is highly misleading - the number of replication cycles before immune response stops further spread is dramatically reduced in a vaccinated person, and therefore both their chances of developing disease, and their chances of passing it on, are severely diminished, and the window of transmission is shortened from days/weeks to hours. So yes, you can theoretically spread it, but once vaccinated you're about as effective at spreading it as a doorknob someone sneezed on, rather than being a walking virus manufacturing factory.

Now, about HIV - HIV is extremely difficult to spread from a single contact (it's got very low virulence) and can be managed very well with treatment, making transmission effectively stop from people in state-of-the-art treatment. However, said treatment is expensive and inconvenient, and has risks of its own, and you need to use it all your life, and it's not available to many people, especially risk groups. By vaccinating people at risk, or large parts of the population, HIV could be eliminated, or dramatically reduced at least, saving the people who would get infected from a life of being medication-dependent, assuming they have access to treatment. So for HIV, a vaccination program won't stop needle sharing and unprotected sex, but will stop people getting even more severe consequences from that. There's a similar vaccination program for hepatitis which has shown excellent results.

> So yes, you can theoretically spread it, but once vaccinated you're about as effective at spreading it as a doorknob someone sneezed on

You should most definitely point out that yours is a conjecture. A reasonable one, but still completely unsupported by clinical data - not because data refutes it, but because there is no data. All trials only examined the reduction of symptomatic infection; they didn't even try to measure whether vaccinated people were able or not to spread the virus.

I would expect your conjecture to be true, but humans are weird, viruses are weird and medicine should be based in evidence, and evidence isn't in yet.

This is true of the large scale vaccine trials, yes. However, there have been several small long term monitoring studies that test immunity persistence post infection recovery, and they seem to show that replication is effectively prevented when exposed to blood serum with acquired immunity with a fairly short time delay (this is what motivated the attempt to do serum transfusions from recovered patients as treatment, but I'm not sure what came of that). That said, you're right that my comparison is overstating the confidence we currently have in this.

Absence of evidence is not evidence of absence. Most scientists fully expect the approved vaccines to prevent infection and transmission for some significant % of people. The only thing that hasn't been conclusively proven is what that % number is.

Not to mention there is already limited/preliminary data that the Moderna vaccine reduces asymptomatic infection (https://www.wsj.com/articles/can-you-still-spread-covid-19-a...).

As I understand it, the reason we don't have that data about the COVID vaccines is that it's costly to check for it. It's much easier to measure symptomatic cases than it is to regularly test everyone in the study to confirm that they don't have an unsymptomatic case. I believe we do think the vaccines prevent COVID, but we just haven't confirmed that.

Any thoughts on whether MRNA is a good stock to buy? They seem to be killing it these days...

My thoughts are you shouldn't buy stocks if your strategy is asking strangers on the internet for tips.

If you want to gamble, just gamble, you don't need anyone's permission.

(Caveat: amateur opinion based on mainstream broad understanding, not an actual scientist.)

This is interesting, but so far a weak first step on flu. Each year experts stare at numbers and perhaps read some tea leaves to choose 4 strains to cover, often missing somewhat.

The innovation I'd like to see: ignore the "choose 4" process, and instead aim to cover all known strains.

>amateur opinion based on mainstream broad understanding

I don’t think experts are reading tea leaves and it’s pretty wild to claim that. There are literally billions of dollars at stake. To bring it bag to software, that’s like me claiming I think machine learning people are just using fancy excel formulas.

> I think machine learning people are just using fancy excel formulas.

I mean... you can do it in excel it is just a lot... slower - you can do like anything in excel


I mean... it's a lot of excel formulas, but still basically excel formulas!

Moderna has a much more flexible production process so should be more resistant to misses.

The experts are not randomly choosing strains. A few years ago it was 3 strains, they recently added a 4th. They could add a 5th next year, or drop back down to 3 depending on what they are seeing actually happen.

The real problem they have is the flu mutates. They know what strains they see now and can add them all easily enough. In the few months between deciding on strains and manufacturing them the flu can mutate to some new strain that wasn't even seen before.

Even if we want to see a more innovative flu vaccine, choosing an iterative approach of getting a working one first, and then fine tuning it to protect against more variants is a good plan.

https://www.sciencemag.org/news/2020/12/innovative-universal... (“Innovative universal flu vaccine shows promise in first clinical test”)

https://www.nature.com/articles/s41591-020-1118-7 (“A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial”)

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