Surveillance studies have shown that bats are reservoirs for SARS-related and other diverse coronaviruses, including SARS-CoV-2, the virus that causes COVID-19 that is believed to have originated in bats. Such zoonotic diseases pose a significant threat to humans. But a future vaccine providing protection against a wide range of coronaviruses may be possible, say Johns Hopkins Medicine researchers, based on findings from their recent study.
In a paper posted online last month in the Journal of Clinical Investigation, the research team evaluated immune response to homologs of the S815-827 peptide—also known as an epitope, which is a protein or portion of a protein that elicits an immune response. These peptides can be found on the SARS-CoV-2 spike protein—which is the target of the mRNA coronavirus vaccines—as well as on the spike proteins of MERS-CoV, the virus that causes Middle East Respiratory Syndrome, and other animal coronaviruses such as those that cause the common cold. Previous studies have shown that these peptides are recognized by infection-fighting immune cells called CD4+ T lymphocytes, which can serve as a measure of how well the immune system responds to a vaccine.
In the first part of their study, the Johns Hopkins Medicine researchers evaluated T cell response to the S815-827 peptide in 38 people who had received two doses of either the Moderna or Pfizer-BioNTech mRNA vaccines. They found that T cells specific to the peptide were produced by 16, or 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, 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."
The researchers then wanted to see if the T cells that recognize and respond to the S815-827 peptide would respond the same way with homologous peptides found on other coronavirus spike proteins—especially for other bat coronaviruses, which are "perceived as the greatest danger for producing another disease transmissible to humans," Blankson says.
The results excited the research team.
"We found that the T cells produced an immune response against the majority of the bat coronaviruses," Blankson says. "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 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.