New discovery could help development of vaccines against future viral diseases from animals to humans

A future vaccine offering 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 the Johns Hopkins Medicine researchers, based on the results of their recent study.

In an article posted online on January 21, 2022, in the Clinical Investigation Journal, the research team focused on a peptide, or protein fragment, on the spike protein of SARS-CoV-2 -; 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 transmitted from camels to humans) and others coronavirus animals. The researchers were particularly interested in studying the S815-827 homologs seen in bat-hosted coronaviruses, as SARS-CoV-2 is thought to have originated from a species of bat. Additionally, bat-borne coronaviruses are considered a major threat to the production of future zoonotic (animal to human) diseases.

Previous research studies of a variety of human coronaviruses that cause the common cold have shown that homologs of the peptide S815-827 -; also known as an epitope (a protein or part of a protein that elicits an immune response) -; are recognized by cells of the immune system that fight infections, called CD4+ T cells.

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

This suggests that a significant portion of the vaccinated population may have T cells that produce an immune response to the epitope. Since this particular component of the spike protein is believed to have an important functional role in SARS-CoV-2 infections and is considered less susceptible to change due to mutations, it is an attractive target for future vaccines -; especially if it can also protect against animal coronaviruses that could migrate to humans.”

Joel Blankson, MD, Ph.D., Study Lead Author, Professor of Medicine, Johns Hopkins University School of Medicine

CD4+ T cells are cells of the immune system, also called T helper cells, because they help another type of immune cell, the B lymphocyte (B cell), to respond to surface proteins -; antigens -; on viruses such as SARS-CoV-2. Activated by CD4+ T cells, immature B cells become either plasma cells that produce antibodies to mark infected cells for elimination from the body, or memory cells that “remember” the biochemical structure of the antigen for a more quick to future infections. Therefore, a CD4+ T cell response can serve as a measure of how the immune system responds to a vaccine and produces humoral immunity.

mRNA vaccines provide genetic instructions for a person’s immune system to recognize the SARS-CoV-2 spike protein and begin producing antibodies against the virus.

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

“Using the lymphocytes we obtained from our study participants, we were able to develop a T-cell line that would only recognize and respond to S815-827 and its homologs,” says Blankson. “We then used a variety of tests to see if these T cells would also recognize epitopes from a number of bat coronaviruses – perceived to be the greatest danger to producing another human-transmissible disease. man.”

The results excited the research team, says Blankson.

“We found that T cells produced an immune response against the majority of bat coronaviruses,” says Blankson. “This supports our hypothesis that current mRNA vaccines elicit T-cell responses that can cross-recognize bat coronaviruses, and therefore may induce some protection against future zoonotic outbreaks.”

In another experiment, Blankson explains, the team showed that the S815-827 homologs of MERS-CoV and a feline coronavirus also triggered epitope-specific CD4+ T cell activity. “This discovery, combined with the main revelation that epitope homologs of 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 coronavirus animals,” says Blankson.

The study was supported by the Johns Hopkins COVID-19 Vaccine-related Research Fund, Bloomberg~Kimmel Institute for Cancer Chemotherapy, Johns Hopkins University Provost, Immune-Viral Landscape in COVID-19-ARDS Pneumonia : 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, members of the Johns Hopkins Medicine study team are lead author Beza Woldemeskel and co-authors Arbor Dykema, Caroline Garliss and Kellie Smith. The co-author of the Hunter College, City University of New York study 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.


Journal reference:

Woldemeskel, BA, et al. (2022) CD4+ T cells from COVID-19 mRNA vaccine recipients recognize a conserved epitope present in various coronaviruses. Clinical Investigation Journal.

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