Here's a full text link [1]. This Letter To The Editor is an incremental contribution to the literature on SARS-CoV-2 antibody dependent enhancement. It does not attempt to quantify the health risks to individuals who have been vaccinated or naturally infected.
> The aim of the present study was to evaluate the recognition of SARS-CoV-2 Delta variants by infection enhancing antibodies directed against the NTD. The antibody studied is 1054 (pdb file #7LAB) which has been isolated from a symptomatic Covid-19 patient.
> Using molecular modelling approaches, we show that enhancing antibodies have a higher affinity for Delta variants than for Wuhan/D614G NTDs
> in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity.
> In conclusion, ADE may occur in people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors) and then exposed to a Delta variant. Although this potential risk has been cleverly anticipated before the massive use of Covid-19 vaccines, the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated.
> It's no longer theoretical that antibody dependent enhancement (ADE) is a concern for the vaccinated
IMO this is too strongly worded and doesn't paint an accurate picture. First of all, ADE is a concern for anyone infected by a virus, whether through vaccination or natural infection. Second, there is substantial literature showing that immune responses can still be protective even in the presence of ADE [1]. Third, OP uses a molecular modelling approach which places it mostly in the realm of theory and far from conclusive clinical evidence.
Some quotes from [1] to support my point:
> It is clear that after many years, and considerable attention, the understanding of ADE of disease after either vaccination or administration of antiviral antibodies is insufficient to confidently predict that a given immune intervention for a viral infection will have negative outcomes in humans.
> Despite the importance that such information would have in the COVID-19 pandemic, in vitro assays do not predict ADE of disease.
> Most animal models of vaccines and antibody interventions show protection, whereas those that suggest potential ADE of disease are not definitive and the precise mechanisms have not been defined.
> Although ADE is a concern, it is also clear that antibodies are a fundamentally important component of protective immunity to all of the pathogens discussed here
> Even when vaccine formulations such as formalin inactivation have shown disease enhancement, neutralizing antibodies with optimized properties have been protective.
An interesting fact: concern about ADE is a significant reason all the vaccines target the spike protein rather than any of the others, such as N (nucleoprotein).
If the author updated the article to include the paper I linked, he could no longer make this claim:
"...and (so far) no sign of ADE even with the variant strains in different parts of the world. We have things to worry about in this pandemic, but as far as I can tell today, antibody-dependent enhancement does not seem to be one of them. I understand why people would worry about it, and want to avoid it. But if you’re coming across reports that say that it’s a real problem right now and that you should avoid getting vaccinated because of it, well, I just don’t see it. Some of that is well-intentioned caution, and some of it is probably flat-out anti-vaccine scaremongering. Anyone with different data or different impressions, well, that’s why the comments are open around here!"
I'ld be curious to see how the author would update the article based on what we see from the molecular modeling in the paper that broke this week.
>First of all, ADE is a concern for anyone infected by a virus, whether through vaccination or natural infection.
That's a false equivalency. Immunity in the unvaccinated but previously infected is broad. The immune system reacted to all parts of the virus, and the variants the unvaccinated were infected with are diverse. In the vaccinated the immunity is narrow, only to the spike protein section of the original Wuhan strain.
It's a reasonable suggestion that the vaccinated are at greater risk of ADE (with very narrow immunity to the original strain's spike protein only) than those infected naturally from a later variant of the entire virus.
Also, the data shows rising COVID cases in areas with more vaccination. I haven't heard a rational explanation for this phenomenon beyond political spin.
Is it really a problem, at least with the Delta variant?
It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill. The protective effect seems to outweigh any infection-enhancing effect.
>It seems quite a few vaccinated people get COVID-19 but it seems very few get seriously ill.
You need to skate where the puck is going. If you look at the data coming out of Israel, which is ahead of everyone else on the curve with vaccinations (and also releases data without manipulating it first, unlike the US - which uses exponentially looser rules for diagnosing COVID in the unvaccinated versus the vaccinated), you get a very different story.
> She said, “This battle is not between the right and the left, it’s not between conservatives and liberals or Republicans and Democrats.” Rather, “this is a battle between Our Lord and the devil,” and every person must choose a side.
...
> She said, “If we treat them early – early is the ticket – with ivermectin and hydroxychloroquine, 80% of the people will not have to go to the hospital.”
> Requiring COVID-19 jabs has become a way to exercise “total control” over people. “They want to force an experimental compound that we really don’t know the long-term effects [of]. Then they want to, on top of that, make sure everyone has a [vaccine] passport. So, it’s total control of a populace. And that’s communism. We’re headed that way,” she said.
This gave me a chuckle and did not inspire confidence.
France is on the brink of a revolution over vaccine passports. Police are inspecting peoples' "papers" at restaurants, and there are anti-passport protests with police leading the parade. There are full blown brownshirt squads in Australia. Police are beating protesters in Canada.
It's not only reasonable to hypothesize this is about control, to me it's irrational to think otherwise at this point.
If you don't like the meta analysis, then sample underlying (cited) studies. I have and didn't find any misrepresentations. Ivermectin looks like a great drug to repurpose as an outpatient therapy for COVID-19.
Not thrilled with that source. But given that Israel has such a high rate of vaccination, it seems reasonable to expect that most of those admitted to hospital at this point will have had the vaccine.
According to the source, the rate of hospitalizations and critical cases is higher amongst the vaccinated, even adjusting for the higher overall vaccination rates. You could make the claim that it isn't age adjusted, but it's hard to make that case when almost all (90%+) of the people being hospitalized are vaccinated, when the general population is ~70% vaccinated.
I agree the source isn't great, but it's hard finding information that hasn't been spun by tech companies at this point. It's worth watching the data coming out of Israel.
So far we haven't seen any evidence of ADE in-vivo. Until that data shows up we shouldn't be jumping to any conclusions based on in-vitro or other computational models.
I disagree that we should wait until we see ADE in the general public before addressing it as a risk. If ADE hits the vaccinated population and is as serious as it was with other viruses, like SARS-1, it will be a catastrophe of biblical proportions.
The CDC changed their guidance with PCR testing so a "breakthrough case" (i.e. a vaccinated person testing positive for COVID) is defined as 28 cycles or fewer, but gave no guidance about changing the PCR cycle count for unvaccinated (which remains in the 35-40 range most places).
This means it takes thousands of times less material to make an unvaccinated person a COVID "case" than a vaccinated person.
>Nowhere in the paper I read that ADE was detected in the vaccined. Vaccine-induced ADE is only evocated as a possibility.
It's literally in the "highlights" of the paper at the top.
"Infection-enhancing antibodies have been detected in symptomatic Covid-19"
From the abstract:
"As the NTD is also targeted by neutralizing antibodies, our data suggest that the balance between neutralizing and facilitating antibodies in vaccinated individuals is in favor of neutralization for the original Wuhan/D614G strain. However, in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity. Thus, ADE may be a concern for people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors)."
First, the line quoted from the highlights section is referring to the 1054 antibody, which was isolated from a patient infected with SARS-CoV-2, as opposed to one produced from vaccine response[1]. Second, the infection enhancing effect was determined in vitro.
So none of that supports the idea that ADE was actually detected in a human, and particularly the idea that vaccine induced ADE has actually been observed.
All that said, if the results of the paper hold up, they may help explain why the efficacy of the vaccines are reduced in the face of the delta variant. That would be extraordinarily useful in formulating better vaccines, so I'm cheering the science along. I'm less cheerful about the cherry-picking to support anti-vaccine narratives.
"In a recent publication, Li et al. (Cell 184 :1-17, 2021) have reported that infection-enhancing antibodies directed against the N-terminal domain (NTD) of the SARS-CoV-2 spike protein facilitate virus infection in vitro, but not in vivo. However, this study was performed with the original Wuhan/D614G strain. Since the Covid-19 pandemic is now dominated with Delta variants, we analyzed the interaction of facilitating antibodies with the NTD of these variants."
I'm sure this post will be taken down shortly, so I wouldn't worry about it.
This is why making vaccines virtually compulsory (eg. France) is a horrible idea. They should be 100% optional. It's very far from obvious taking one now is a good idea. It helps with delta, but new variants that evolve in response to pro-ADE selective pressure may be extremely dangerous to the vaccinated.
Infected vaccinated people are variant factories, because they have same [1] [2] viral loads as unvaccinated, but less severe symptoms (for the delta strain) - meaning infected unvaccinated are much more likely to self-isolate fast, while vaccinated may not even know they have covid. We already know current vaccines are borderline worthless [3] in preventing delta infections - Pfizer is only 39% effective.
In addition to that, selective pressure for new variants with more severe ADE doesn't exist inside people without antibodies because newly mutated strain has no competitive advantage. This means a new variant with severe ADE is almost certainly going to originate from a vaccinated person.
Immunity from a past infection is more selective [4] which is very good as far as ADE risk is concerned, so the main risk is from current vaccines.
Last but not least, policies that encourage 100% vaccinated environments (covid passes) create a perfect environment for a new ADE variant to preferentially spread - also because people there feel safe so they don't care about masks and social distancing.
Trading a negligible risk from current covid strains for a potential risk of a very lethal ADE variant (eg. 5% for the vaccinated in the otherwise healthy 30-40 range) in the future should be an individual decision. Even from a population survival perspective it's better to have a heterogeneous population.
"there was no significant difference between the Ct values of samples collected from breakthrough cases and the other cases. This might mean that the viral load of vaccinated and unvaccinated persons infected with SARS-CoV-2 is also similar."
"Data from COVID-19 tests in the United States, the United Kingdom and Singapore are showing that vaccinated people who become infected with Delta SARS-CoV-2 can carry as much virus in their nose as do unvaccinated people."
As I understand it, only mods have the ability to update submission titles. You can email them using the Contact link in the footer.
The guidelines include guidelines around submission titles. I don't know the title you submitted, but in my experience, mods edit titles to make them more in keeping with the guidelines. Often (but not always) they include a comment that they did edit it. But, if you've got a question about it, you can ask by email. They don't always see comments.
Normally antibodies help neutralize and protect against viral infections. Antibody-dependent enhancement (ADE) is a phenomenon in which antibodies actually enhance the ability of the virus to infect and replicate. This can cause more severe symptoms and poor health outcomes. In can happen to anyone infected with the virus, regardless of vaccination or naturally acquired immunity.
Historically some vaccine candidates that targeted coronaviruses, RSV virus and Dengue virus elicited vaccine associated ADE. Naturally there has been some concern that current COVID-19 vaccines will result in ADE. So far the scientific literature has not established any consensus that the risk of ADE outweighs the benefits of COVID-19 vaccines. In fact, much of the existing literature supports the idea that the protective effects of vaccination or natural infection will outweigh the risks of ADE. Still in rare cases some individuals will be severely impacted by ADE, so for now it is something to at least be aware of.
> So far the scientific literature has not established any conclusion on the risk of ADE with respect to COVID-19 vaccines.
This may be understating the evidence. Derek Lowe cites this paper[1] with the conclusion "did any of these show ADE hints during their development? And are any of them showing signs of it now? The short answers: they did not."
> The aim of the present study was to evaluate the recognition of SARS-CoV-2 Delta variants by infection enhancing antibodies directed against the NTD. The antibody studied is 1054 (pdb file #7LAB) which has been isolated from a symptomatic Covid-19 patient.
> Using molecular modelling approaches, we show that enhancing antibodies have a higher affinity for Delta variants than for Wuhan/D614G NTDs
> in the case of the Delta variant, neutralizing antibodies have a decreased affinity for the spike protein, whereas facilitating antibodies display a strikingly increased affinity.
> In conclusion, ADE may occur in people receiving vaccines based on the original Wuhan strain spike sequence (either mRNA or viral vectors) and then exposed to a Delta variant. Although this potential risk has been cleverly anticipated before the massive use of Covid-19 vaccines, the ability of SARS-CoV-2 antibodies to mediate infection enhancement in vivo has never been formally demonstrated.
[1] Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination? https://www.journalofinfection.com/article/S0163-4453(21)003...