
Coronavirus Vaccine Prospects - hprotagonist
https://blogs.sciencemag.org/pipeline/archives/2020/04/15/coronavirus-vaccine-prospects
======
btilly
For those who don't recognize the author, he is a well-known biochemist
working in pharmaceuticals whose blogs are generally very well informed and
well worth the read.

Also sometimes extremely funny. Read
[https://blogs.sciencemag.org/pipeline/archives/category/thin...](https://blogs.sciencemag.org/pipeline/archives/category/things-
i-wont-work-with) for good examples of that.

~~~
danieltillett
I think Derek might object to being called a biochemist - he is actually an
organic chemist by training.

~~~
btilly
Ah. Thanks for the correction.

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truantbuick
I'd like to believe we will start mass manufacturing all promising candidates
long before testing is complete.

The stakes are so high this time that it's important _as soon as_ testing
results are deemed adequate, they can start distributing them, even if it
means manufacturing stuff that doesn't ultimately pan out.

~~~
folli
You need to have some selection beforehand. There's not enough manufacturing
capacity to go around.

~~~
randomsearch
Worse: a WHO official (apologies to trump supporters) said that you can’t
divert much capacity because that risks causing outbreaks of other diseases.
So have to create a lot of new capacity.

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ignoramous
I want to point out that 5 vaccines (out of 78) are in phase 1 trials (4 of
those actively looking for volunteers, visit clinicaltrials.gov links below to
see if you qualify):

1\. mRNA-1273 (lipid nanoparticle encapsulated mRNA vaccine encoding S
protein) by Moderna:
[https://clinicaltrials.gov/ct2/show/NCT04283461](https://clinicaltrials.gov/ct2/show/NCT04283461)

2\. Ad5-nCoV (Adenovirus type 5 vector that expresses S protein) by CanSino
Biologicals: NCT04313127.

3\. INO-4800 (DNA plasmid encoding S protein delivered by electroporation) by
Inovio Pharmaceuticals:
[https://clinicaltrials.gov/ct2/show/record/NCT04336410](https://clinicaltrials.gov/ct2/show/record/NCT04336410)

4\. LV-SMENP-DC (Dendritic cell modified with lentiviral vector expressing
synthetic minigene based on domains of selected viral proteins; administered
with antigen-specific cytotoxic T lymphocyte) by Shenzhen Geno-Immune Medical
Institute:
[https://clinicaltrials.gov/ct2/show/NCT04276896](https://clinicaltrials.gov/ct2/show/NCT04276896)

5\. Pathogen-specific artificial antigen-presenting cell (aAPCs modified with
lentiviral vector expressing synthetic minigene based on domains of selected
viral proteins) by Shenzhen Geno-Immune Medical Institute:
[https://clinicaltrials.gov/ct2/show/NCT04299724](https://clinicaltrials.gov/ct2/show/NCT04299724)

Ref:
[https://www.nature.com/articles/d41573-020-00073-5](https://www.nature.com/articles/d41573-020-00073-5)

------
jdsully
The history of rushed vaccines is not good. The first attempt at a polio
vaccine was rushed through with inadequate safety measures and resulted in
40,000 children getting sick, some with permanent paralysis.

There are good reasons vaccines take years to be approved. I’m very worried
we’ll see a repeat of historical mistakes in the current rush.

[https://en.m.wikipedia.org/wiki/Cutter_Laboratories#The_Cutt...](https://en.m.wikipedia.org/wiki/Cutter_Laboratories#The_Cutter_incident)

~~~
danieltillett
No that it matters, but it wasn’t a safety issue with the vaccine, but a
manufacturing issue. The vaccine was perfectly safe, it just wasn’t
manufactured to the correct specification.

~~~
jdsully
The method of manufacture is part of the FDA approval

~~~
danieltillett
Yes it is, but if it isn’t followed then you can’t blame the vaccine. Many
other companies made the same vaccine using the same processes without issue.
The Salk vaccine is very safe if manufactured to specification.

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whoisjuan
I might be wrong, but I thought any human trial needs at least a full one-year
follow-up to make sure that the vaccine didn't cause any damage, side effects,
reactions, etc, and that indeed created long term immunity.

It seems to me that rushing the timelines potentially opens up a lot of risks
for post-vaccine side effects. Doesn't it?

~~~
technotony
That's what the article says, human trials in fall this year and then a
regulatory filing a year later. There is basically no chance of a vaccine for
this being widely available before 2022. That assumes that one of these
vaccines works, despite no vaccine for a coronavirus ever passing regulatory
approval (hence this is a hard problem, and plenty of incentive to vaccinate
against things like common cold which would be a nice money earner for a
someone).

~~~
Bombthecat
I laugh every time someone telling me we will have something by winter... We
will live with quarantine and social distincing for quit for a while.

~~~
ignoramous
We might yet have a vaccine in 6 months (optimistically) [0] though 12 to 18
months is much more realistic. Different categories of vaccines have different
manufacturing and safety profiles [1] depending on which we a vaccine
candidate might be approved sooner than expected, especially since 3 novel,
previously untested platforms have made it to clinical trials, already.

[0] _Even if shortcuts ... can be found, it is unlikely that a vaccine would
be available earlier than 6 months after the initiation of clinical trials.
Realistically, SARS-CoV-2 vaccines will not be available for another 12–18
months._ From:
[https://www.cell.com/immunity/fulltext/S1074-7613(20)30120-5...](https://www.cell.com/immunity/fulltext/S1074-7613\(20\)30120-5#%20)

[1]
[https://www.cell.com/action/showFullTableHTML?isHtml=true&ta...](https://www.cell.com/action/showFullTableHTML?isHtml=true&tableId=tbl1&pii=S1074-7613%2820%2930120-5)

------
guidedlight
I do wonder how effective and safe an old-fashioned inoculation could be in
the absence of a vaccine.

A small quantity of the virus could be introduced to your leg where it is away
from your lungs and bloodstream. Your body could fight the virus there.

~~~
vikramkr
That's a type of vaccine. If you want to figure out how safe and effective it
is, you need to run a clinical trial. Same as amy other vaccine. If you got
started now, you'd be running behind some of the other approaches that are
already in clinical trials, so, um, get started fast?

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Leary
On the off chance that China develops a working vaccine first, how could
America ensure its safety?

~~~
phyrex
The exact same way as with every other vaccine from any other country.

~~~
sean2
I don't know what inspired GP's question, but I think he's getting at the fact
that China is known to be faking their numbers from the beginning of the
outbreak to show how effective the leaders are in combating the virus. So, in
reality, we have no idea whether their methods are successful or not. Same
with a vaccine, if China reports an extremely effective vaccine, available
immediately, invented thanks to Xi's vision and leadership; Then do we just
start using it here in the US, or do we have another year of hiding in our
houses while we run trials while the rest of the credulous world gets back to
work?

~~~
perl4ever
"China is known to be faking their numbers"

I haven't seen an explanation of South Korea then. Are they faking their
statistics too? If not, then China's reported stats don't seem so incredible.

~~~
TeMPOraL
Personally I haven't even seen a more detailed accusation than "China is
faking their numbers [because they obviously are, they're China]" \- that is,
other than flat-Earth level "oh look at the mobile phone number cancellation
data that's definitely trustworthy and definitely indicates people being
erased".

Not to mention any attempts at quantifying what's the level of the alleged
manipulation of the data. Is it suspected to be undercounted by an order of
magnitude? Two orders? Three orders? Why?

~~~
dntbnmpls
It's Gordon Chang-style propaganda. Before this, it was china was faking their
economic data. China was a house of cards about to collapse. I guess all the
chinese made iphones, computers, everything was not real either.

------
3fe9a03ccd14ca5
> _Roughly estimated, even a seasonal flu vaccine might kill about one out of
> every ten million recipients though such a reaction – we give it to everyone
> possible, though, because far more people will die if we don’t._

Yeah that’s frightening, but really true? I’ve never heard of a single person
dying from the flu vaccine locally.

------
yread
The numbers involved are just so hard to imagine. Even if we create a vaccine
as safe as flu shot it will kill on the order of 1000 people worldwide
(1:10m). We have to hope that they will be randomly distributed and not the
first volunteers who take it...

~~~
jobseeker990
There's also a good chance we might force this on people against their will
(If the current panic is any indication.)

~~~
nick_kline
Look at the current death rates. Requiring a tested vaccine is a reasonable
response. Requiring an untested vaccination is not something I see happening.
I guess we could get to "you can't do certain things like go to large
gatherings" if you don't have the vaccine or evidence of having had it.

Meanwhile, In the US 12.x k people at a minimum died of this in the last 7
days, doubling the previous total deaths. There's also a much higher death
rate overall than in the past, many of those must be related to covid-19 [1].
If current trends follw, In another week the 25,000 total current deaths will
double, in other words, 25,000 are on track to die of covid in a week. It's
not just new york; from that same site, in the last 7 days new york's total
went from 7k to 15k total cumulative deaths - new york is still doubling every
week, even though they look to slow down.

The deadly statistics are fantastically interesting. NY itself had about 8k
net new deaths the last week, the rest of the us had about 10k. Both are
doubling on a weekly basis.

1\. [https://covidtracking.com/data/us-
daily](https://covidtracking.com/data/us-daily)

------
sjg007
I worry that the vaccine won't be effective. To stop this coronavirus we
basically have to quarantine and stop human activity for a few months. We are
already down that rabbit hole so we just need to stay the course and really
isolate as much as we can. The govt is going to have to help people to get
through the next 6 months.

~~~
12elephant
So what happens when we end quarantine in 6 months? We'll just have a COVID
epidemic 6 months from now. Isolation does not stop the spead, it only slows
the spread.

As soon as isolation is lifted, whether that be in a month or 10 years, the
spread will resume. Unless of course either a) herd immunity is developed or
b) a vaccine is developed.

We've only ever eradicated one infectious disease in all of human history
(smallpox) and we had a vaccine for that. See:
[https://www.historyofvaccines.org/index.php/content/articles...](https://www.historyofvaccines.org/index.php/content/articles/disease-
eradication)

~~~
sjg007
Well, no, if you have enough isolation then the virus runs out of hosts. It
goes extinct unless it can survive latently or in some other host species. If
we are getting infected by bats consistently then we are in trouble.

~~~
12elephant
That's wishful thinking. The virus will survive in Africa, or India, or many
of the other places that are incapable or unwilling to enforcing a complete
lockdown (many of these places are in the US itself).

As I mentioned above, we have only ever erradicated _one_ infectious disease
in all of human history. The chances of COVID, with its highly infectious
nature, being the second are quite slim.

Just like the first outbreak, all it takes is one person with the virus to
start the whole process over again.

~~~
sjg007
Yeah, it goes along with strong border control.

All international travel is going to be restricted for a very long time
regardless of antibody and PCR tests.

------
LyndsySimon
As a lay person, I found this to be a very informative article.

One thing I didn't see mentioned was a recent article that caught my attention
- apparently, tobacco may be used as means of production for a potential
vaccine [0].

Given that the linked article was published on April 1, I initially thought it
to be satire. Upon further consideration, though, it not only seems to be
genuine but it makes sense: tobacco is likely one of the best understood
plants from a genetic standpoint, with a long history of successful genetic
modification using both traditional and modern approaches. It's certainly one
of the best understood that also has large-scale production capabilities, and
I would imagine that the tobacco industry has more incentive than most to seek
the positive PR that this could bring.

Finally, setting aside the greater political context, it seems to me that the
FDA under the Trump administration is more flexible and risk-tolerant than any
point in my lifetime (and perhaps in living memory). There are certainly many
challenges that will have to be overcome before we get to the point that we're
able to widely roll out an effective vaccine, but I strongly suspect that this
flexibility will result in a speed of development and approval that will
surprise many of us. Of course, that speed will come with associated risks,
but that's just the nature of things.

I would not be surprised to see widespread voluntary human testing of
promising vaccine candidates in the next six months - perhaps even sooner if a
promising candidate ends up being derived from the past few years' work in
creating a vaccine for SARS-CoV-1.

0: [https://www.dailymail.co.uk/news/article-8175855/BAT-
claims-...](https://www.dailymail.co.uk/news/article-8175855/BAT-claims-
Covid-19-vaccine-breakthrough-using-tobacco-plants.html)

~~~
avgDev
I am really concerned about the fact that the FDA is trying to fast track
stuff.

I just want to offer a perspective of why this is dangerous. We are having
some serious issues with flouroquinolone antibiotics. The side-effects of the
medication are insane and under-reported. 9 years ago I was given the
antibiotic for an infection, my body went into shock, I was released the next
day with some odd neurological issues. None of it reported to the FDA, few
months later I got tendon pain. I go to mayo clinic, they disagree the
antibiotic caused it. Seen 30+ physicians in the span of 2 years, 2 agreed
that it is possible. One of them said to wait it out, and refused to actually
put it in my chart. The antibiotics carry a 'black label' and clearly state
side effects may occur up to 1 year. I reported it to the FDA, then I found
groups of people suffering from chronic fatigue, tendon raptures, weird
neurological symptoms, some had diagnosis of 'fibromyalgia', some had chronic
tendinitis, yet after reviewing their medical information they found they took
a flouroquinolone antibiotic but nobody ever even suggested that it could be
that.

This bring me to Tamiflu fiasco. Governments have spent billions of dollars to
purchase Tamiflu to fight the flu. Later reports came out about issues with
the studies, the maker picking positive studies and withholding neutral or
negative information. It has not proven much better than the drugs we already
use to treat the flu.

Fast tracking a medication can have terrible results, cost billions of
dollars, and cripple hundreds of people. Doing any scientific research with
panic in the back of your mind and high pressure from politicians and people
is dangerous IMO. Especially, in a profit driven healthcare system.

~~~
xyzzyz
_Fast tracking a medication can have terrible results, cost billions of
dollars, and cripple hundreds of people._

All of this is true, and yet in our current situation, _not_ fast tracking can
have even worse results, cost _trillions_ of dollars and _kill millions_ of
people.

~~~
avgDev
It is a difficult situation, but the cure should not be worse than the
disease. I just offered my perspective. I am not an expert in medical
research, and hope that qualified people can do their jobs and find a safe
treatment/vaccine. However, I am scared that people that say 'No' will be
silenced or removed, kind of like people in Theranos, who were experts in
their fields.

