A new paper in Methods and protocols of biology, published by Oxford University Press, shows that it is possible to design vaccines that will induce a stronger immune response to infectious pathogens, such as the virus that causes COVID-19. In this study, the authors proposed and tested a new bioinformatics approach and tool that allows researchers to select parts of proteins that will trigger a strong immune response. Vaccines developed based on this approach would offer better protection against diseases.
The immune system of humans (and other vertebrates) distinguishes between self and non-self structures to attack and destroy the latter. T cells are the part of the immune system responsible for this recognition. They do this by identifying peptides, short chains of amino acidswhich are present in non-self proteins, for example, in the proteins of a virus or a bacterium, but absent in the proteins of a host, such as man.
To avoid recognition by T cells of a host, parasitic organisms remove all unnecessary peptides from their proteins. In particular, they mutate these peptides to mimic those present in the proteins of their host species.
In this study, the researchers tested a critical prediction of the peptide mimicry theory: they investigated whether they could predict the ability of a parasite’s proteins to cause immune response based on the content of peptides absent in the body of their host. Building on previous detailed mapping of SARS-CoV-2-related T cell clones, they explored the points of intersection between the list of actual T cell response targets and a list of potential T cell recognition targets, peptides present in SARS-CoV-2 but absent from the human body.
Computer simulations showed that real T-cell recognition targets had a significantly higher proportion of pentapeptides and hexapeptides (peptides composed of five and six amino acids respectively) that are not found in human proteins. The new method, based on immunological theory, was four times more effective at detecting targets in the case of SARS-CoV-2 than currently used methods based on empirical observations.
The authors believe the method will allow researchers to develop more effective vaccines, specifically designed to recognize and target the parts of parasite proteins that trigger the strongest immune responses.
“Our theory of peptide mimicry, which explores how a parasite adapts its peptide vocabulary to that of its host, began primarily as a basic research effort,” said the paper’s lead author, Jaroslav Flegr.
“However, in exploring this topic, we discovered that it could also have wide practical implications, such as in the field of vaccine construction. We hope our findings will deepen our understanding of disease course and pathogen transmission and provide valuable insights into improving vaccine design and the broader control of infectious diseases.
More information:
Jaroslav Flegr et al, Exposing and Exploiting Host-Parasite Arms Race Clues in SARS-CoV-2: A Principally New Method for Improved T-cell Immunogenicity Prediction, Biology methods and protocols (2023). DOI: 10.1093/biomethods/bpad011 , academic.oup.com/biomethods/ar … 3/biomethods/bpad011
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