SARS-CoV-2 protein targeted by immune cells also triggers response in
bat coronaviruses, study shows
Finding may help in development of vaccines against future animal-to-
human viral diseases

Date:
February 16, 2022
Source:
Johns Hopkins Medicine
Summary:
A future vaccine providing protection against a wide range of
coronaviruses that jump from their original animal hosts to humans -
- including SARS-CoV-2, the cause of COVID-19 -- may be possible,
say researchers.



FULL STORY ==========================================================================
A future vaccine providing protection against a wide range of
coronaviruses that jump from their original animal hosts to humans --
including SARS-CoV-2, the cause of COVID-19 -- may be possible, say Johns Hopkins Medicine researchers, based on findings from their recent study.


==========================================================================
In a paper posted online Jan. 21, 2022, in the Journal of Clinical Investigation, the research team focused on a peptide, or protein
fragment, on the SARS-CoV-2 spike protein -- the target of the
two available messenger RNA (mRNA) vaccines for COVID-19 -- called
S815-827. Homologs (equivalent peptides) can be found on the spike
proteins of MERS-CoV (the virus that causes Middle East Respiratory
Syndrome, more commonly known as MERS, and believed to have been passed
from camels to humans) and other animal coronaviruses. The researchers
were particularly interested in studying the S815-827 homologs seen in coronaviruses hosted by bats because SARS-CoV-2 is believed to have risen
from a bat species. Additionally, bat-borne coronaviruses are considered
a major threat for producing future zoonotic (animal-to-human) diseases.

Previous research studies looking at a variety of human coronaviruses
that cause the common cold have shown that homologs of the S815-827
peptide -- also known as an epitope (a protein or portion of a protein
that elicits an immune response) -- are recognized by infection-fighting
cells of the immune system called CD4+ T lymphocytes.

In the first part of their study, the Johns Hopkins Medicine researchers evaluated T cell response to the S815-827 epitope in 38 people who
had received two doses of either the Moderna or Pfizer-BioNTech mRNA
vaccines against SARS- CoV-2. They found that T cells specific to the
peptide were produced by 16 (42%) of the study participants.

"This suggests that a significant portion of the vaccinated population
might have T cells that produce an immune response to the epitope," says
study senior author Joel Blankson, M.D., Ph.D., professor of medicine at
the Johns Hopkins University School of Medicine. "Since this particular
spike protein component is believed to have an important functional
role in SARS-CoV-2 infections and is considered less likely to change
because of mutations, it's an appealing target for future vaccines -- especially if it also can protect against animal coronaviruses that
might migrate to humans." CD4+ T lymphocytes are immune system cells,
also known as helper T cells, because they assist another type of immune
cell, the B lymphocyte (B cell), in responding to surface proteins --
antigens -- on viruses such as SARS-CoV-2.

Activated by the CD4+ T cells, immature B cells become either plasma
cells that produce antibodies to mark infected cells for disposal from
the body, or memory cells that "remember" the antigen's biochemical
structure for a faster response to future infections. Therefore, a CD4+
T cell response can serve as a measure of how well the immune system
responds to a vaccine and yields humoral immunity.



==========================================================================
The mRNA vaccines provide genetic instructions to a person's immune
system to recognize the SARS-CoV-2 spike protein and start production
of antibodies against the virus.

Since S815-827 -- a very stable component of the SARS-CoV-2 spike
protein - - potentially is a more specific target for future vaccines,
the researchers wanted to see if the epitope-specific T cells (ones that recognize and respond to S815-827) they found in their vaccinated study participants would act the same with the homologous peptides found on
other coronavirus spike proteins.

"Using the lymphocytes we obtained from our study participants, we were
able to grow a line of T cells that would only recognize and respond
to S815-827 and its homologs," says Blankson. "We then used a variety
of tests to see if those T cells also would recognize the epitopes on
a number of bat coronaviruses - - perceived as the greatest danger for producing another disease transmissible to humans." The results excited
the research team, Blankson says.

"We found that the T cells produced an immune response against the
majority of the bat coronaviruses," says Blankson. "This supports
our hypothesis that the current mRNA vaccines elicit T cell responses
that can cross-recognize bat coronaviruses, and thus might induce some protection against future zoonotic outbreaks." In another experiment,
says Blankson, the team showed that the S815-827 homologs for MERS-CoV
and a feline coronavirus also triggered epitope-specific CD4+ T cell
activity. "This finding, combined with the main revelation that epitope homologs for many bat coronaviruses stimulate an immune response, means
that we may one day be able to develop a multivalent vaccine that could
protect against a broad spectrum of animal coronaviruses," says Blankson.



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The study was supported by the Johns Hopkins COVID-19 Vaccine-related
Research Fund, the Bloomberg~Kimmel Institute for Cancer Chemotherapy,
the Johns Hopkins University provost, the Immune-Viral Landscape in
COVID-19 Pneumonia-ARDS: IVAR Study and three grants from the National Institutes of Health (NIH): NIH Cancer Center Support Grant P30 CA006973,
grant U54CA260492 and grant R37CA251447.

Along with Blankson, the members of the study team from Johns Hopkins
Medicine are lead author Beza Woldemeskel and co-authors Arbor Dykema,
Caroline Garliss and Kellie Smith. Study co-author from Hunter College,
City University of New York, is Saphira Cherfils.

Blankson, Dykema and Smith have filed for patent protection on subsets
of the technologies described in the study. Smith receives commercial
research funding from Bristol-Myers Squibb, AstraZeneca and Enara Bio,
and has received travel support and honoraria from Illumina Inc.

All other study authors report no conflicts of interest.

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


========================================================================== Journal Reference:
1. Bezawit A. Woldemeskel, Arbor G. Dykema, Caroline Garliss, Saphira
Cherfils, Kellie N. Smith, Joel N. Blankson. CD4+ T-cells from
COVID-19 mRNA vaccine recipients recognize a conserved epitope
present in diverse coronaviruses. Journal of Clinical Investigation,
2022; DOI: 10.1172/ JCI156083 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220216121828.htm

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