Study details robust T-cell response to mRNA COVID-19 vaccines -- a more durable source of protection
Results underline the importance of a second dose and include
implications for booster shots

Date:
August 16, 2021
Source:
University of Pennsylvania School of Medicine
Summary:
Messenger-RNA (mRNA) vaccines against the coronavirus that causes
COVID- 19 provoke a swift and strong response by the immune system's
T cells - - the heavy armor of the immune system, according to a
new study.



FULL STORY ========================================================================== Messenger-RNA (mRNA) vaccines against the coronavirus that causes
COVID-19 provoke a swift and strong response by the immune system's T
cells -- the heavy armor of the immune system -- according to a study
from researchers in the Perelman School of Medicine at the University
of Pennsylvania. Although recent studies of vaccines tend to focus on
the antibody response, the T-cell response is also an important and
potentially more durable source of protection -- yet little has been
reported so far on the T-cell response to COVID-19 vaccines.


==========================================================================
In the new study, which appears in the journal Immunity, the Penn
Medicine researchers analyzed the T-cell responses in 47 healthy people
who received two doses of the Moderna and Pfizer/BioNTech mRNA vaccines.

The results reveal the complex details of how the T-cell response to these vaccines unfolds, and underline the importance of a second dose for people
with no history of COVID-19. The findings showed, however, that in people
with a history of COVID-19, the T-cell response was already robust after
the first vaccine dose, with no significant increase after the second
dose, which may have implications for potential future booster shots.

"Our findings underscore the fact that we need to look at T cells, not
just antibodies, if we want a complete picture of the vaccine response
for those who have not had COIVD-19 and for those who have recovered
from the disease," said senior author E. John Wherry, PhD, chair of the department of Systems Pharmacology and Translational Therapeutics and
director of the Penn Institute of Immunology in the Perelman School of
Medicine at the University of Pennsylvania.

Antibodies are forked proteins secreted by immune cells called B cells;
they can bind tightly to specific viral structures on virus-infected
cells. T cells also have antibody-like receptors that enable tight binding
to specific viral structures, but they are whole cells, some of which --
called "killer" T-cells -- are capable of directly killing virus-infected
cells they encounter. T cells therefore have long been regarded as the
heavy armor of the immune system.

Their responses to vaccines are harder to study than antibody responses, though, so less is known about those responses, including in the case
of COVID- 19.

Researchers examined in detail the T-cell responses to mRNA vaccination
in 36 healthy people who had no history of COVID-19, and 11 people who
had previously recovered from COVID-19.

In the group of participants who did not previously have COVID-19, they
found that the first vaccine dose elicited a rapid and strong response
from helper T cells called CD4 T cells -- some of which help marshal
an antibody response, while others stimulate the proliferation of CD8
killer T cells. The strengths of those initial CD4 T cell responses
generally predicted the later strengths of antibody and killer T-cell responses. However, the killer T cells tended not to appear in large
numbers until after the second vaccine dose -- confirming the importance
of that second dose for people with no COVID-19 history.

By contrast, in the prior-COVID-19 group, helper and killer T cells
specific for the COVID-19 coronavirus were already substantially
present before the first dose. After that first dose, T cell numbers
rose somewhat, but did not significantly increase after the second dose.

"For people who haven't had COVID-19, the first dose powerfully primes
the pump, and the second dose turns on the whole engine -- but having
had COVID-19 is like having had that first vaccine dose already,"
Wherry said. "It is important to point out, however, that a complete understanding of the relative importance of these T cell responses,
compared to antibody, in protection from future infections will require
larger clinical studies." The results also showed that the T-cell
response in the weeks after mRNA vaccination includes T-cell types
normally elicited by natural infection -- and in general, natural viral infection is known to be capable of inducing T-cell protection that
lasts years and even decades.

"We need to do follow-up studies to confirm the longevity of the T-cell response to vaccination, but our results here support the idea that that response can be long-lasting," Wherry said.

Support for the research was provided by the National Institutes of Health (AI105343, AI082630, AI108545, AI155577, AI149680, AI152236, AI082630, HL143613, P30-AI0450080, T32 AR076951-01, T32 CA009140, T32 AI055400, U19AI082630), the Allen Institute for Immunology, the Cancer Research Institute, the Chen Family Research Fund, the Parker Institute for
Cancer Immunotherapy, the Penn Center for Research on Coronavirus and
Other Emerging Pathogens, the University of Pennsylvania Perelman School
of Medicine COVID Fund, the University of Pennsylvania Perelman School
of Medicine 21st Century Scholar Fund, and Jeffrey Lurie, Joel Embiid,
Josh Harris, and David Blitzer.

========================================================================== Story Source: Materials provided by University_of_Pennsylvania_School_of_Medicine. Note: Content may be
edited for style and length.


========================================================================== Journal Reference:
1. Mark M. Painter, Divij Mathew, Rishi R. Goel, Sokratis
A. Apostolidis,
Ajinkya Pattekar, Oliva Kuthuru, Amy E. Baxter, Ramin S. Herati,
Derek A.

Oldridge, Sigrid Gouma, Philip Hicks, Sarah Dysinger, Kendall A.

Lundgreen, Leticia Kuri-Cervantes, Sharon Adamski, Amanda Hicks,
Scott Korte, Josephine R. Giles, Madison E. Weirick, Christopher
M. McAllister, Jeanette Dougherty, Sherea Long, Kurt D'Andrea, Jacob
T. Hamilton, Michael R. Betts, Paul Bates, Scott E. Hensley, Alba
Grifoni, Daniela Weiskopf, Alessandro Sette, Allison R. Greenplate,
E. John Wherry. Rapid induction of antigen-specific CD4+ T cells is
associated with coordinated humoral and cellular immune responses
to SARS-CoV-2 mRNA vaccination.

Immunity, 2021; DOI: 10.1016/j.immuni.2021.08.001 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/08/210816143933.htm

--- up 14 weeks, 3 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)