Study Recommends Bioinformatic Vaccine Design

New research published by Oxford University Press in Biology Methods & Protocols suggests that it may be able to build a vaccine that triggers a higher immune response to invading pathogens, such as the virus that causes COVID-19. The authors devised and evaluated a new bioinformatic approach and tool in this study that allows researchers to choose protein portions that will provoke a significant immune response. Vaccines created using this approach would provide superior disease protection.

Human (and other vertebrate) immune systems distinguish between self and non-self structures in order to target and kill the latter. T cells are the immune system component responsible for this identification. They accomplish this by detecting peptides, which are short chains of amino acids that are found in non-self proteins, such as viruses or bacteria, but not in host proteins, such as humans.

Parasitic organisms remove all superfluous peptides from their proteins to prevent identification by a host’s T cells. They specifically modify these peptides to imitate those found in the proteins of their host species.

The researchers examined a major assumption of peptide mimicry theory in this study: if they could anticipate the potential of a parasite’s proteins to elicit an immune response based on the content of peptides missing from their hosts’ bodies. Building on previous extensive mapping of SARS-CoV-2-related T-cell clones, they investigated the points of intersection between the list of real T-cell response targets and a list of possible T-cell recognition targets, peptides found in SARS-CoV-2 but not in the human body.

Computer simulations revealed that the actual T-cell recognition targets contained a substantially larger proportion of pentapeptides and hexapeptides (peptides with five and six amino acids, respectively), which were not found in human proteins. The novel strategy, based on immunological theory, was four times more effective than current methods based on empirical observations in finding the targets in the case of SARS-CoV-2.

The scientists believe that the technology will enable researchers to create more effective vaccinations that are particularly designed to recognize and target the regions of parasite proteins that elicit the strongest immune responses.

“Our peptide mimicry theory, which delves into how a parasite adapts its peptide vocabulary to that of its host, began primarily as a fundamental research endeavor,” said the paper’s lead author, Jaroslav Flegr.

“However, as we’ve explored this topic, we’ve discovered that it might also have extensive practical implications, such as in the field of vaccine construction. We hope our findings will deepen our understanding of disease evolution and pathogen transmission and provide valuable insights in the enhancement of vaccine design and the broader fight against infectious diseases.”

Source Link