Could anyone explain the significance of this finding?
Researchers mix diluted blood plasma with viral samples, and then see whether it can grow in cell cultures. They figure out the concentration of plasma needed to neutralize all the virus.
2 doses of the vaccine produces plasma that can still neutralize the virus, but it requires 20x as much plasma on average. In turn, this means that the virus is more likely to be able to replicate and infect new cells before all the virus is neutralized.
However:
- There is still antibody efficacy against the virus, just not nearly as much.
- Memory B cells have a head-start at further developing specific immunity to new variants.
- This ignores the effect of T-cell mediated immunity.
- This mentions evidence that people who were previously infected and vaccinated have good neutralizing titers against Omicron.
- Other evidence suggests people who are boosted have much better neutralization titers against Omicron. That is, boosting doesn't just increase the number of antibodies, but increases the breadth of antibody protection.
Is there any way to know whether that increased breadth of antibody protection isn't coming from a post vaccination exposure that wasn't tested for not tested? Since vaccinated people aren't generally required to do asymptomatic testing, let alone symptomatic testing in many places.
It's complicated! The short answer I gave elsewhere: B cells aggressively replicate and mutate in response to pathogens, and those that match are selected for. Repeating this process gets more B cells, but also broader varieties of resultant antibodies matching not just the original pathogen but things that are close to it.
> Is there any way to know whether that increased breadth of antibody protection isn't coming from a post vaccination exposure that wasn't tested for not tested?
Yes. We collect plasma from people, and then test it against a variety of variants in assays. We have plenty of old plasma to do this with.
Indeed, there's some evidence that many people who were both infected with SARS-CoV-1 and subsequently vaccinated against SARS-CoV-2 may have exceptionally broad immunity to coronaviruses, not isolated to just SARS-CoV variants but also to wild-type coronaviruses circulating in animals and human coronaviruses causing the common cold.
> they select for the spike protein of the original variant and ignore others
Repeated exposure causes you to get many different kinds of antibodies that react against many things like the original spike protein. There's ample research showing that a 2 shot (and 3 shot) series of mRNA vaccination creates a very broad response that cross-reacts to many spike protein variants.
Reaction against the spike protein is best, because this binding doesn't just activate the rest of the immune system, but it's neutralizing against the virus: it prevents its entry into cells.
Compare this figure:
https://cdn.jamanetwork.com/ama/content_public/journal/jama/...
Many convalescent (prior infected) individuals had very low neutralization activity against variants. All vaccinated individuals had good neutralization titers against all variants measured in this study, though they were still definitely better against A.1 than other types.
> whereas natural infection generates a broader response that will target a variety of proteins.
Natural infection will generate a variety of nucleocapsid antibodies, too (against non-spike portions of the virus).
This is a mixed bag: it means the immune system can be activated and it also means that the immune system will try and break down things that have antibodies bound elsewhere on the virus... but the spike antibodies around that could directly prevent infection of new cells are less effective against variants.
And as for immunity from infection, your body makes antibodies for the prefusion spike (the free floating form that infects cells), the post fusion spike (after it binds to ACE2), and the nucleocapsid. Since prefusion spikes are what bind to cells for entry, you’d want your immune system focused entirely on attacking that vector. China’s sinovac vaccine generates nucleocapsid antibodies and it’s failing in the face of omicron.
Against Delta, if you compare a vaccinated population with 2 doses of the mRNA vaccine against an equivalent unvaccinated population that ended up with 100 infections, with about 70 people having symptoms and 10 people with severe illness, you'd expect:
* 60 people who would have otherwise been infected to show no evidence of infection. That is, the vaccine is so strongly neutralizing that a large proportion of people that would otherwise be infected show no evidence of virtal replication at all.
* Another 30 people or so to end up infected, without symptoms. The virus replicated some in their cells, but the severity of the disease before an immune response was mounted was so low that it went unnoticed. Note that this number has not changed too much from the unvaccinated population.
* About 10 people with symptoms, of whom 1 has severe illness.
You could view this as mostly shifting severity "downwards" -- some people who would have been infected ending up not; some people who would have had symptoms instead just being infected; some people who would have had severe illness instead just having symptoms.
From a pure mechanical view: if an infected cell produces 1000 copies of the virus, ordinarily resulting in 50 other cells being infected... and antibodies from a vaccine glom up on spike proteins and reduce this 50 number to 10-- the virus still grows in your body, but the rest of your immune system has a whole lot longer to react before illness becomes severe. And this ignores other benefits from vaccination (earlier mobilization of immune system, T-cell mediated immunity, training of B cell lines to target spike proteins resulting in faster maturation of variant-specific antibodies, etc). So even if the antibody concentration and affinity isn't quite sufficient it's still a benefit.
The opposite is the case.
No vetting of that Israeli study, no peer review, no competent efforts to account for bias in the sample, and it just does not hold up to scrutiny when compared to other results.
32.39 cases / 100,000 people double vaccinated vs 31.93 / 100k of the unvaccinated.
https://covid-19.ontario.ca/data?fbclid=IwAR2pRUq9GN9EEoDTm0...
The vaccines don't seem to confer any lasting difference.
One concern with observational studies: people who choose vaccination don't behave exactly the same as people who don't. They may assume more risks out of perceived safety. They may also be more likely to test or seek medical care. This is why, at a minimum, you need case control to start to believe the conclusions.
In any case, we have actual case control studies showing mRNA vaccine efficacy against illness and particularly against severe illness from Omicron. They disagree on the amounts, and in some cases the numbers are not thrilling (30%), but there's no studies so far implying no efficacy.
The study we're discussing here concludes its abstract with: "These data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained."
I think you could give out 2 doses of a strong laxative and show it statistically protects sick people against covid too. If you take out the weakest, the rest will seem to do better.
Edit: Disclaimer at the top of the page says technical difficulty.
The effect is caused by the age data ending in mid-October, before the spike we're looking at in mid-December. So, the age-segregated data couldn't show that spike at all.
Why would we expect vaccine derived coronavirus-19 immunity to be substantially longer than natural other-coronavirus immunity, which we know to be months, not years.
That is, we know of many vaccines where the protection from vaccination is greater than the protection from prior infection. It looks like that is true of COVID vaccines, both by observational / case control data and from data comparing antibody neutralizing titers between convalescent plasma and vaccinated individuals.. e.g. https://cdn.jamanetwork.com/ama/content_public/journal/jama/...
For any given patient--- who knows. There could be one person somewhere who'd get no benefit from vaccination and a huge benefit from prior infection. We can only know about the superiority of vaccination to prior infection in aggregate, but the effect is real.
Edit to add: the fact that vaccine + previous natural infection has a better immune response over just the vaccine likely has to do with the rest of the virus being more similar to older variants of the virus and your body recognizing some other part of the virus versus the spike itself.
This may be a factor. But, repeated exposure means more breadth of antibodies. B cells aggressively replicate and mutate in response to pathogens, and those that match are selected for. Repeating this process gets more B cells, but also broader varieties of resultant antibodies matching not just the original pathogen but things that are close to it. This is why:
* 1 dose of mRNA was pretty effective against B.1.1.7, but not very effective against Delta, which had some immune escape mutations.
* 2 doses of mRNA vaccines targeted at B.1.1.7 were pretty effective against Delta, but only slightly effective against Omicron, which had a lot of (different) immune escape mutations.
* 3 doses of mRNA vaccines targeted at B.1.1.7 seem pretty effective against Omicron.
That being said, I'm going off the preliminary study that shows that vaccine >= infection for older variants whereas vaccine + infection >> vaccine for omicron.
As an aside, I've got three shots of Moderna in me and I caught omicron during the covidtastrophe a few weeks ago. It was extremely mild but I'm now resigned to the idea that vaccines are an assurance against getting actually sick more than a silver bullet.
More exposure basically means broader protection-- whether it's exposure through infection, vaccination, etc.
Whatever you're exposed to, the compliment and quantity of antibodies widens and is drawn towards whatever you're exposed to. You end up with antibodies that bind against whatever you're exposed to in many different ways-- many of which will be cross-reactive against other variants.
Obviously, it'd be nice if we had a omicron-based booster, because it would be broadening the protection more in that direction.
> As an aside, I've got three shots of Moderna in me and I caught omicron during the covidtastrophe a few weeks ago.
Sorry to hear that. We still have relatively little data, but it looks our best current guesses are:
* Vs. Delta: 2 doses of Pfizer/Moderna: about 60-70% effective against infection, 80-90% effective against symptoms, and 95%+ effective against severe illness.
* Vs. Omicron: 2 doses of Pfizer/Moderna: ???% (poor) effective against infection, 30% effective against symptoms, 50-70% effective against severe illness. 3 doses of Pfizer/Moderna: ???% (maybe moderate) efficacy against infection, 60%??? effective against symptoms (evidence quality poor), 85% effective against severe illness. It also looks like this is short lived and sloping down relatively fast.
In any case, you're protected every step of the way: Less likely to become infected, less likely to become symptomatic if infected, and less likely to develop severe illness if symptomatic.
One interesting epidemiological question is: vaccinated people are pretty likely to be asymptomatic with Omicron, so they may be more likely to spread it.
On the other hand, these "leaky vaccines" have already prevented a massive amount of mortality. Yes, the duration and quality of protection, even boosted, against Omicron is unfortunate... but even 2 doses can still be expected to save a high number of lives from Omicron.
Here's also some analysis about this effect with Omicron, which seems honest about the limitations: https://boriquagato.substack.com/p/theres-something-antigeni...
This is not supported by any evidence.
(4 in 18 months with boosters every decade)
Are you up to date on your boosters for DPT? I don't know anyone who has maintained that.
Though this is only looking at the drop in vaccine efficacy with respect to symptomatic infections, two shots of an mRNA still might give decent protection against severe disease; don't know if there is a change with this.
There's not. Severe disease is caused by your body attacking your own lungs because the virus did so much damage between initial infection and your body recognizing the problem. Vaccines, any vaccine, dramatically shortens the time between initial infection and immune response. Shorter duration == less damage to your body in that time.
I think the "reasonable effectiveness" part speaks for itself. My reading of the "provided high neutralization capacity" part is that, we know vaccines lose effectiveness over time, so the "reasonable effectiveness" has a caveat of "provided you get a booster, and possibly regular boosters in the future".