Current vaccines teach T cells to fight Omicron
Study shows how the fully vaccinated respond to a range of SARS-CoV-
2 variants

Date:
January 24, 2022
Source:
La Jolla Institute for Immunology
Summary:
Scientists have found that four COVID-19 vaccines prompt the body
to make effective, long-lasting T cells against SARS-CoV-2. These
T cells can recognize SARS-CoV-2 Variants of Concern, including
Delta and Omicron.



FULL STORY ========================================================================== Scientists at La Jolla Institute for Immunology (LJI) have found that
four COVID-19 vaccines (Pfizer-BioNTech, Moderna, J&J/Janssen, and
Novavax) prompt the body to make effective, long-lasting T cells against SARS-CoV-2. These T cells can recognize SARS-CoV-2 Variants of Concern, including Delta and Omicron.


==========================================================================
"The vast majority of T cell responses are still effective against
Omicron," says LJI Professor and study co-leader Alessandro Sette,
Dr. Biol.Sci.

"These cells won't stop you from getting infected, but in many cases
they are likely to keep you from getting very ill," adds LJI Professor
Shane Crotty, Ph.D.

"And this is true in all the type of vaccines we studied -- and up to
six months after vaccination," says LJI Instructor Alba Grifoni, Ph.D.,
who co-led the work with Sette and Crotty.

These data come from adults who were fully vaccinated, but not yet
boosted. The researchers are now investigating T cell responses in boosted individuals and people who have experienced "breakthrough" COVID-19 cases.

The new Cell study also shows that fully vaccinated people have
fewer memory B cells and neutralizing antibodies against the Omicron
variant. This finding is in line with initial reports of waning immunity
from laboratories around the world.



========================================================================== Without enough neutralizing antibodies, Omicron is more likely to cause a breakthrough infection. Fewer memory B cells means the body will then be
slower to churn out additional neutralizing antibodies to fight the virus.

"Most of the neutralizing antibodies, i.e., the antibodies that work
well against SARS-CoV-2, bind to a region called the receptor binding
domain, or RBD," says LJI Instructor Camila Coelho, Ph.D., who served as co-first author of the study. "Our study revealed that the 15 mutations
present in Omicron RBD can considerably reduce the binding capacity of
memory B cells, compared to other SARS-CoV-2 variants such as Alpha,
Beta and Delta." How T cells fight Omicron The good news is that
neutralizing antibodies and memory B cells are just two arms of the
body's adaptive immune response. In a person exposed to SARS-CoV-2,
T cells do not prevent infection. Instead, T cells patrol the body and
destroy cells that are already infected, which prevents a virus from multiplying and causing severe disease.

The LJI team believes the "second line of defense" from T cells helps
explain why Omicron infections are less likely to lead to severe
disease in fully vaccinated people. (The variant is also appears to
infect different tissues) To know whether the vaccine-induced T cells
they detected in their study were actually effective against variants
such as Delta and Omicron, the scientists took a close look at how the
T cells responded to different viral "epitopes."


========================================================================== Every virus is made up of proteins that form a certain shape or
architecture. A viral epitope is a specific landmark on this architecture
that T cells have been trained to recognize. The current COVID-19 vaccines
were designed to teach the immune system to recognize specific epitopes
on the initial "Alpha" variant of SARS-CoV-2. As the virus has mutated,
its architecture has changed, and the concern is that immune cells will
no longer recognize their targets.

The new study shows that while the architecture of Omicron is different
enough to evade some neutralizing antibodies and memory B cells, memory
T cells still do a good job of recognizing their targets, even on the
highly mutated Omicron variant. Overall, at least 83 percent of the CD4+ (helper) T cell responses and 85 percent of the CD8+ T cell responses
stayed the same, no matter the vaccine or the variant.

Crotty notes that the memory B cells that do bind Omicron are likely to
also contribute to protection against severe disease. "Vaccinated people
have memory CD4+ T cells, CD8+ T cells, and memory B cells to help fight
the infection if the virus gets past the initial antibodies, and having multiple lines of defense is likely an important strength," Crotty says.

Omicron is still a threat The researchers emphasize that no one should
count on T cell protection alone.

The LJI study sheds light on immunity at the population level, but
individual immune responses vary, and relying on one's untested immune
system to fight COVID is a roll of the dice.

"I'd urge people to still be cautious and keep wearing masks," says
Alison Tarke, a graduate student and member of the Sette Lab who served
as co-first author with Coelho. "There is a chance you are one of the
few people with a declining immune response." "This work also emphasizes
the importance of getting a booster," adds Sette.

(Find a booster near you) The Sette and Crotty Labs have teamed up on
COVID-19 research since early 2020.

With the Sette Lab's expertise in T cells and the Crotty Lab's expertise
in vaccine design and B cell responses, the collaboration has led to
key insights into pre-existing SARS-CoV-2 immunity, vaccine responses,
severe COVID cases and more.

Grifoni says the researchers are now looking at two pressing
questions. First, they'd like to see what T cells, B cells and antibody responses look like after COVID-19 booster shots. Second, they are investigating what the immune response looks like after a breakthrough infection. (Volunteer for an LJI Clinical Study) Additional authors
of the study, "SARS-CoV-2 vaccination induces immunological memory
able to cross-recognize variants from Alpha to Omicron," are co-first
author Zeli Zhang, co-first author Jennifer M. Dan, Esther Dawen Yu,
Nils Methot, Nathaniel I. Bloom, Benjamin Goodwin, Elizabeth Phillips,
Simon Mallal, John Sidney, Gilberto Filaci, Daniela Weiskopf and Ricardo
da Silva Antunes.

This research was supported by the National Institutes of Health's
National Institute of Allergy and Infectious Diseases (contracts
No. 75N93021C00016 to A.S. and 75N9301900065) and a PhD student fellowship through the Clinical and Experimental Immunology Course at the University
of Genoa, Italy.

========================================================================== Story Source: Materials provided by
La_Jolla_Institute_for_Immunology. Original written by Madeline McCurry-Schmidt. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Alison Tarke, Camila H. Coelho, Zeli Zhang, Jennifer M. Dan,
Esther Dawen
Yu, Nils Methot, Nathaniel I. Bloom, Benjamin Goodwin, Elizabeth
Phillips, Simon Mallal, John Sidney, Gilberto Filaci, Daniela
Weiskopf, Ricardo da Silva Antunes, Shane Crotty, Alba Grifoni,
Alessandro Sette.

SARS-CoV-2 vaccination induces immunological T cell memory able
to cross- recognize variants from Alpha to Omicron. Cell, 2022;
DOI: 10.1016/ j.cell.2022.01.015 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220124151101.htm

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