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Immunity Generated from Covid-19 Vaccines Differs from an Infection

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Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#11
post #4

If you are wondering whether you are sufficiently protected by having recovered from COVID, this article provides up to date answers. Get vaccinated. Get a booster if recommended.

You are being unfairly downvoted, because what you are saying runs contrary to people's gut feelings.

At this point, we have enough statistics on people getting COVID a second time with or without vaccination, to know that vaccination reduces your odds of re-infection by ~2.3. [1]

[1] https://www.cdc.gov/mmwr/volumes/70/wr/mm7032e1.htm

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#12
post #7

> antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. I wonder how this might impact the design of future mRNA vaccines. For example, could vaccines target multiple proteins that both are associated with the virus?

this is referred to as a polyvalent vaccine, and it is a good thing to do once we understand enough about the antigens in question to incorporate both in one shot. There is nothing of course precluding two different vaccines of differenct valence, and we have been doing this for a short time now, when we combine single jab mRna vaccines, with adenoviral vectored vaccines, there is very slight sequence variation between adV and mRNA vaccines however by strictest interpretation this is a multivalant[bivalant] scenario.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#13
post #8

It would be interesting to see the duration of the immunity or resistance across multiple vaccine variants. The latest data from the UK indicates that the AZ vaccine suffers less degradation over time than Pfizer, at least when it comes to the Delta variant which is now the prevalent one in the UK. Israel has now giving boosters to 30 year olds and older in order to boost the immunity to infection and resistance to s…

My understanding is that it may be due to the difference of time during the two shots. It's possible that 2 weeks between the two shots of Pfizer is too short. We're learning.

In the UK Pfizer and AZ both are on 8 weeks protocols and the UK has seen a sharper drop in Pfizer efficacy compared to AZ.

I got Pfizer in the UK, I also suspect to have had it in March (3 days of some coughing and loss of smell), I’m under 40 so no AZ for me.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#14

Antigen targets aside, there is also a difference in the production of antibodies in the mucosal system. Current vaccines are intra muscular and lacks a robust mucosal response while natural infection will provide mucosal immunity as well. As one can imagine, mucosal immunity is very important in an upper respiratory track disease w.r.t. symptomatic infection and transmission.

Yeah, why aren't we putting more effort into getting an intranasal vaccine approved for emergency use? An intranasal vaccine would confer mucosal immunity and might also be more acceptable to the vaccine hesitant. They're talking about 3rd shot boosters, but I'd really like to be able to get an intranasal vaccine as the third booster.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#15
Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the nose, sinuses, or throat. This is the disparity many studies are now highlighting but failing to acknowledge the cause of.

The required next step is intranasal vaccination to recruit B and T cells to the upper respiratory mucosa and have the B cells produce local IgA antibodies. This would actually stop infections (infections defined from nasal swab testing).

It is up to the NIH and other large organizations in the world to get this messaging out there. There are two types of "breakthrough". There's the fact that intramuscular vaccinations don't protect the upper respiratory mucosa, and then there's the very rare cases when sars-cov-2 actually manages to infect body organs and the lower lungs. They are entirely different things.

The variants currently circulating don't play a huge role in this discrepancy. We'd be seeing the same amount of upper respiratory mucosa infections (not hospitalizations) even if there were no delta and it was just alpha/beta/gamma or even original wuhan sequence sars-cov-2.

ref: https://www.gov.uk/government/publications/long-term-evoluti... page 5, #8. "Whilst we feel that current vaccines are excellent for reducing the risk of hospital admission and disease, we propose that research be focused on vaccines that also induce high and durable levels of mucosal immunity in order to reduce infection of and transmission from vaccinated individuals. This could also reduce the possibility of variant selection in vaccinated individuals."

ref: https://science.sciencemag.org/content/373/6553/397 "the ideal vaccination strategy may use an intramuscular vaccine to elicit a long-lived systemic IgG response and a broad repertoire of central memory B and T cells, followed by an intranasal booster that recruits memory B and T cells to the nasal passages and further guides their differentiation toward mucosal protection, including IgA secretion and tissue-resident memory cells in the respiratory tract."

ref: https://www.nature.com/articles/s41577-021-00550-x

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#16

The spike protein targeting antibodies produced by the vaccine do indeed target a wider range of spike mutations than the spike protein antibodies from previous infection. However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Isra…

That really depends on which vaccine. There are several inactivated virus vaccines such as Sinovac used in other countries which we would expect to produce antibodies for more than just the spike protein. However it's unclear whether those vaccines are more or less effective in practice.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#17

Intramuscular vaccinations are the most important first step and will keep hospitalization down. But intramuscular vaccination for respiratory viruses does not provide long lasting immunity to the surface mucosa tissues of the upper respiratory tract. The IgG antibodies in body serum do seep into the lower lungs and provide robust protection from serious disease, but they do not prevent infections very long in the no…

Why isn't there more of a push for emergency use of intranasal vaccines? Apparently there are some in the testing phase, but I think if they were given as much resources as the mRNA vaccines were we might have already had an intranasal vaccine in use by now. The Israelis have one in testing but it still sounds like it's a long ways off from being deployed on a large scale. The other advantage of an intransal vaccine is that we might be able to convince a portion of the vaccine hesitant to get it.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#18
post #8

It would be interesting to see the duration of the immunity or resistance across multiple vaccine variants. The latest data from the UK indicates that the AZ vaccine suffers less degradation over time than Pfizer, at least when it comes to the Delta variant which is now the prevalent one in the UK. Israel has now giving boosters to 30 year olds and older in order to boost the immunity to infection and resistance to s…

My understanding is that it may be due to the difference of time during the two shots. It's possible that 2 weeks between the two shots of Pfizer is too short. We're learning.

In part due to immunity duration concerns and, honestly, in part due to supply issues - Canada ended up going way wide on vaccines - most people ended up with twelve weeks between vaccinations.

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#19

The spike protein targeting antibodies produced by the vaccine do indeed target a wider range of spike mutations than the spike protein antibodies from previous infection. However, vaccines only target spike protein, while a previous infection will cause your body to produce antibodies for a much larger set of targets on the virus, which in practice leads to a more robust immunity. This is supported by data from Isra…

I was confused about that as well. The article suggests that targeting "other portions of the spike protein" (as immune systems previously infected with COVID do) results in the immune system being _less_ robust against variants of the virus than targeting "places on the RBD" (as immune systems exposed to Moderna's mRNA vaccine do):

> Specifically, antibodies elicited by the mRNA vaccine were more focused to the RBD compared to antibodies elicited by an infection, which more often targeted other portions of the spike protein. Importantly, the vaccine-elicited antibodies targeted a broader range of places on the RBD than those elicited by natural infection.

> These findings suggest that natural immunity and vaccine-generated immunity to SARS-CoV-2 will differ in how they recognize new viral variants. What’s more, antibodies acquired with the help of a vaccine may be more likely to target new SARS-CoV-2 variants potently, even when the variants carry new mutations in the RBD.

Anyone with more experience in immunology care to weigh in on why the second paragraph there follows from the first? Naively, one might expect targeting a wider variety of places on on the COVID spike protein to result in better immunity against variants, not worse. Why is the article saying the opposite?

Re: Immunity Generated from Covid-19 Vaccines Differs from an Infection

#20

Antigen targets aside, there is also a difference in the production of antibodies in the mucosal system. Current vaccines are intra muscular and lacks a robust mucosal response while natural infection will provide mucosal immunity as well. As one can imagine, mucosal immunity is very important in an upper respiratory track disease w.r.t. symptomatic infection and transmission.

Yeah, why aren't we putting more effort into getting an intranasal vaccine approved for emergency use? An intranasal vaccine would confer mucosal immunity and might also be more acceptable to the vaccine hesitant. They're talking about 3rd shot boosters, but I'd really like to be able to get an intranasal vaccine as the third booster.

Nasal vaccine trials are underway. We should have preliminary results in a few months.

https://www.medpagetoday.com/special-reports/exclusives/9252...

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