Newswise — A recent publication in Biology Methods & Protocols, issued by Oxford University Press, presents a promising breakthrough in vaccine design. The study suggests that it may be feasible to create vaccines capable of inducing a more robust immune response against infectious pathogens, including the virus responsible for COVID-19. The authors of this research have introduced and examined a novel bioinformatic approach and tool that empowers researchers to selectively target specific segments of proteins capable of triggering a potent immune response. By leveraging this innovative strategy, vaccines developed could offer enhanced protection against various diseases.

The immune system of humans and other vertebrates possesses the remarkable ability to distinguish between self and non-self structures, enabling it to combat and eliminate the latter. Central to this recognition process are T cells, which play a pivotal role in identifying peptides—short chains of amino acids—found in non-self proteins, such as those belonging to viruses or bacteria, while being absent in the host's own proteins. To evade detection by the host's T cells, parasitic organisms strategically eliminate any unnecessary peptides from their proteins. Specifically, they mutate these peptides to closely resemble those present in the host's proteins, effectively camouflaging themselves from the immune response.

In this research, the scientists put the peptide mimicry theory to the test by examining whether they could predict a parasite's ability to elicit an immune response based on the absence of certain peptides in their host's bodies. Drawing from earlier detailed mapping of T-cell clones related to SARS-CoV-2, they investigated the overlapping points between the actual T-cell response targets and a list of potential T-cell recognition targets—peptides present in SARS-CoV-2 but not found in the human body.

Using computer simulations, they found that the actual T-cell recognition targets contained a notably higher proportion of pentapeptides and hexapeptides (peptides consisting of five and six amino acids, respectively) that were not present in human proteins. This novel method, founded on immunological theory, exhibited four times greater efficiency in detecting these targets in the case of SARS-CoV-2 compared to current empirical observation-based methods. The authors are optimistic that this approach will enable researchers to develop more effective vaccines, precisely tailored to recognize and target the specific parts of parasite proteins that trigger the most robust immune responses.

Jaroslav Flegr, the lead author of the paper, explained that their peptide mimicry theory initially originated as a fundamental research pursuit. Its primary aim was to investigate how a parasite adapts its peptide language to that of its host. However, as they delved deeper into this subject, they stumbled upon its potential practical implications, particularly in the realm of vaccine development. They are hopeful that their findings will not only contribute to a better understanding of disease evolution and pathogen transmission but also offer valuable insights to improve vaccine design and strengthen the global efforts in combating infectious diseases.

Journal Link: Biology Methods and Protocols