[ExI] COVID super immunity

[Sherry Knepper]

And how can it be certain the immunity is permanent, meaning if the person dies it will not be from COVID-19?

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  On Sat, Oct 23, 2021 at 1:16 AM, Sherry Knepper<guessmyneeds at yahoo.com> wrote:   
But how many shots are needed for the vaccine requirement for the 100% covid19 immunity?
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  On Thu, Oct 21, 2021 at 1:02 PM, Stuart LaForge via extropy-chat<extropy-chat at lists.extropy.org> wrote:   
According this article in Nature, people who have caught and survived  
COVID infection and subsequently get the COVID vaccine develop super  
immunity aka hybrid immunity. This super immunity protects the patient  
against every POSSIBLE COVID strain. They tested this by creating  
every possible mutation of the viral spike protein and testing patient  
antibodies against them. People who are super immune seem protected  
against all strains of COVID past, present, and future. Scientists are  
hoping a third vaccine dose creates the same kind of super immunity as  
having recovered the disease and getting vaccinated.

https://www.nature.com/articles/d41586-021-02795-x

Around a year ago — before Delta and other variants entered the  
COVID-19 lexicon — virologists Theodora Hatziioannou and Paul  
Bieniasz, both at the Rockefeller University in New York City, set out  
to make a version of a key SARS-CoV-2 protein with the ability to  
dodge all the infection-blocking antibodies our body makes.

The goal was to identify the parts of spike — the protein SARS-CoV-2  
uses to infect cells — that are targeted by these neutralizing  
antibodies in order to map a key part of our body's attack on the  
virus. So the researchers mixed and matched potentially concerning  
mutations identified in lab experiments and circulating viruses, and  
tested their Franken-spikes in harmless ‘pseudotype’ viruses incapable  
of causing COVID-19. In a study published this September in Nature1,  
they reported that a spike mutant containing 20 changes was fully  
resistant to neutralizing antibodies made by most of the people tested  
who had been either infected or vaccinated — but not to everyone’s.

Those who had recovered from COVID-19 months before receiving their  
jabs harboured antibodies capable of defanging the mutant spike, which  
displays much more resistance to immune attack than any known  
naturally occurring variant. These peoples’ antibodies even blocked  
other types of coronaviruses. “It’s very likely they will be effective  
against any future variant that SARS-CoV-2 throws against them,” says  
Hatziioannou.

As the world watches out for new coronavirus variants, the basis of  
such ‘super-immunity’ has become one of the pandemic’s great  
mysteries. Researchers hope that, by mapping the differences between  
the immune protection that comes from infection compared with that  
from vaccination, they can chart a safer path to this higher level of  
protection.

“It has implications on boosters and how our immune responses are  
primed for the next variant that emerges,” says Mehul Suthar, a  
virologist at Emory University in Atlanta, Georgia. “We’re flying by  
the seat of our pants trying to figure this stuff out.”

Hybrid immunity
Not long after countries began rolling out vaccines, researchers  
started noticing unique properties of the vaccine responses of people  
who had previously caught and recovered from COVID-19. “We saw that  
the antibodies come up to these astronomical levels that outpace what  
you get from two doses of vaccine alone,” says Rishi Goel, an  
immunologist at the University of Pennsylvania in Philadelphia who is  
part of a team studying super-immunity — or ‘hybrid immunity’, as most  
scientists call it.

Initial studies of people with hybrid immunity found that their serum  
— the antibody-containing portion of blood — was far better able to  
neutralize immune-evading strains, such as the Beta variant identified  
in South Africa, and other coronaviruses, compared with ‘naive’  
vaccinated individuals who had never encountered SARS-CoV-22. It  
wasn’t clear whether this was just due to the high levels of  
neutralizing antibodies, or to other properties.

The most recent studies suggest that hybrid immunity is, at least  
partly, due to immune players called memory B cells. The bulk of  
antibodies made after infection or vaccination come from short-lived  
cells called plasmablasts, and antibody levels fall when these cells  
inevitably die off. Once plasmablasts are gone, the main source of  
antibodies becomes much rarer memory B cells that are triggered by  
either infection or vaccination.


International COVID-19 trial to restart with focus on immune responses

Some of these long-lived cells make higher-quality antibodies than  
plasmablasts, says Michel Nussenzweig, an immunologist at the  
Rockefeller. That’s because they evolve in organs called lymph nodes,  
gaining mutations that help them to bind more tightly to the spike  
protein over time. When people who recovered from COVID-19 are  
re-exposed to SARS-CoV-2’s spike, these cells multiply and churn out  
more of these highly potent antibodies.

“You get a sniff of antigen, in this case of mRNA vaccine, and those  
cells just explode,” says Goel. In this way, a first vaccine dose in  
someone who has previously been infected is doing the same job as a  
second dose in someone who has never had COVID-19.

Potent antibodies
Differences between the memory B cells triggered by infection and  
those triggered by vaccination — as well as the antibodies they make —  
might also underlie the heightened responses of hybrid immunity.  
Infection and vaccination expose the spike protein to the immune  
system in vastly different ways, Nussenzweig says.

In a series of studies3,4,5, Nussenzweig’s team, which includes  
Hatziioannou and Bieniasz, compared the antibody responses of infected  
and vaccinated people. Both lead to the establishment of memory B  
cells that make antibodies that have evolved to become more potent,  
but the researchers suggest this occurs to a greater extent after  
infection.

The team isolated hundreds of memory B cells — each making a unique  
antibody — from people at various time points after infection and  
vaccination. Natural infection triggered antibodies that continued to  
grow in potency and their breadth against variants for a year after  
infection, whereas most of those elicited by vaccination seemed to  
stop changing in the weeks after a second dose. Memory B cells that  
evolved after infection were also more likely than those from  
vaccination to make antibodies that block immune-evading variants such  
as Beta and Delta.

Health-care workers get the Pfizer-BioNTech COVID-19 vaccination in  
Portland, Oregon.
Health-care workers receiving the Pfizer–BioNTech COVID-19 vaccine.  
People who get the vaccine after infection are less likely to test  
positive for COVID-19 than individuals with no history of  
infection.Credit: Paula Bronstein/Getty

A separate study found that, compared with mRNA vaccination, infection  
leads to a pool of antibodies that recognize variants more evenly by  
targeting diverse regions of spike6. The researchers also found that  
people with hybrid immunity produced consistently higher levels of  
antibodies, compared with never-infected vaccinated people, for up to  
seven months. Antibody levels were also more stable in people with  
hybrid immunity, reports the team led by immunologist Duane Wesemann  
at Harvard Medical School in Boston, Massachusetts.

‘Not surprising’
Many studies of hybrid immunity haven’t followed naive vaccine  
recipients for as long as those who recovered from COVID-19, and it’s  
possible their B cells will make antibodies that gain potency and  
breadth with more time, additional vaccine doses, or both, researchers  
say. It can take months for a stable pool of memory B cells to  
establish itself and mature.

“It’s not surprising that people infected and vaccinated are getting a  
nice response,” says Ali Ellebedy, a B-cell immunologist at Washington  
University in St. Louis, Missouri. “We are comparing someone who  
started the race three to four months ago to someone who started the  
race now.”

There is some evidence that people who received both jabs without  
previously being infected seem to be catching up. Ellebedy’s team  
collected lymph-node samples from mRNA-vaccinated individuals and  
found signs that some of their memory B cells triggered by the  
vaccination were gaining mutations, up to 12 weeks after the second  
dose, that enabled them to recognize diverse coronaviruses, including  
some that cause common colds7.

Goel, University of Pennsylvania immunologist John Wherry and their  
colleagues found signs that six months after vaccination, memory B  
cells from naive individuals were continuing to grow in number and  
evolve greater capacity to neutralize variants8. Antibody levels fell  
after vaccination, but these cells should start cranking out  
antibodies if they encounter SARS-CoV-2 again. “The reality is you  
have a pool of high-quality memory B cells that are there to protect  
you if you ever see this antigen again,” Goel says.

Booster benefits
A third vaccine dose might allow people who haven't been infected to  
achieve the benefits of hybrid immunity, says Matthieu Mahévas, an  
immunologist at the Necker Institute for Sick Children in Paris. His  
team found that some of the memory B cells from naive vaccine  
recipients could recognize Beta and Delta, two months after  
vaccination9. “When you boost this pool, you can clearly imagine you  
will generate potent neutralizing antibodies against variants,”  
Mahévas says.

Extending the interval between vaccine doses could also mimic aspects  
of hybrid immunity. In 2021, amid scarce vaccine supplies and a surge  
in cases, officials in the Canadian province of Quebec recommended a  
16-week interval between first and second doses (since reduced to 8  
weeks).

A team co-led by Andrés Finzi, a virologist at the University of  
Montreal, Canada, found that people who received this regimen had  
SARS-CoV-2 antibody levels similar to those in people with hybrid  
immunity10. These antibodies could neutralize a swathe of SARS-CoV-2  
variants — as well as the virus behind the 2002–04 SARS epidemic. “We  
are able to bring naive people to almost the same level as previously  
infected and vaccinated, which is our gold standard,” says Finzi.


How ‘killer’ T cells could boost COVID immunity in face of new variants

Understanding the mechanism behind hybrid immunity will be key to  
emulating it, say scientists. The latest studies focus on antibody  
responses made by B cells, and it’s likely that T-cell responses to  
vaccination and infection behave differently. Natural infection also  
triggers responses against viral proteins other than spike — the  
target of most vaccines. Nussenzweig wonders whether other factors  
unique to natural infection are crucial. During infection, hundreds of  
millions of viral particles populate the airways, encountering immune  
cells that regularly visit nearby lymph nodes, where memory B cells  
mature. Viral proteins stick around in the gut of some people months  
after recovery, and it’s possible that this persistence helps B cells  
hone their responses to SARS-CoV-2.

Researchers say that it is also important to determine the real-world  
effects of hybrid immunity. A study from Qatar suggests that people  
who get Pfizer–BioNTech’s mRNA vaccine after infection are less likely  
to test positive for COVID-19 than are individuals with no history of  
infection11. Hybrid immunity might also be responsible for falling  
case numbers across South America, says Gonzalo Bello Bentancor, a  
virologist at the Oswaldo Cruz Institute in Rio de Janeiro, Brazil.  
Many South American countries experienced very high infection rates  
earlier in the pandemic, but have now vaccinated a large proportion of  
their populations. It's possible that hybrid immunity is better than  
the immunity from vaccination alone at blocking transmission, says  
Bello Bentancor.

As breakthrough infections caused by the Delta variant stack up,  
researchers including Nussenzweig are keen to study the immunity in  
people who were infected after their COVID-19 vaccinations, rather  
than before. An individual’s first exposure to influenza virus biases  
their responses to subsequent exposures and vaccinations — a  
phenomenon called original antigenic sin — and researchers want to  
know if this occurs with SARS-CoV-2.

Those studying hybrid immunity stress that — whatever the potential  
benefits — the risks of a SARS-CoV-2 infection mean that it should be  
avoided. “We are not inviting anybody to get infected and then  
vaccinated to have a good response,” says Finzi. “Because some of them  
will not make it through.”

Nature 598, 393-394 (2021)

doi: https://doi.org/10.1038/d41586-021-02795-x

Stuart LaForge


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