To develop diagnostics and vaccines that detect and prevent covid-19, scientists research the presence of HLA genes, which expose the virus to the body’s defense cells, in populations around the world. There were few records from South America and, for that reason, an international survey with the participation of FMVZ (USP School of Veterinary Medicine and Zootechnics (University of São Paulo) collected genetic information from the South American population to expand the database on genes. From this survey, the study identified the parts of the virus most likely to be identified by the HLA genes, which will be essential in the creation of diagnostic kits and specific vaccines for use in the region.
The HLA (acronym for human leukocyte antigen) genes express proteins on the surfaces of human cells that recognize and display the proteins (antigens) of the pathogens to the cells of the immune system, a process known as “presentation of antigens”. “It allows defense cells such as T lymphocytes to eliminate cells infected by pathogens such as the covid-19 virus,” says geneticist and biotechnologist Ruy Diego Chacón, a researcher at FMVZ who participated in the study. “At the same time, there is also the activation of other important defense cells, B lymphocytes, the production of antibodies capable of neutralizing the virus and also the generation of immune memory, which would increase the immune response against new infections by the virus.”
According to the researcher, the most used HLA gene database in the world, the Allele Frequency Net Database, has little information about South America. “To meet this limitation, we surveyed more than 2,000 genetic studies and generated updated and more representative information on the most common gene variations in the countries of the region”, he highlights. “We were able to update the records on more than 12 million new data, mainly in the case of Brazil, where the increase was approximately 2,300 times.”
The information gathered in the research was used to identify, using computational techniques, the potential immunogenic epitopes in the proteins of the new coronavirus (SARS-CoV-2) more similar to the variants of the HLA genes existing in South America. “The epitopes, too called antigenic determinants, they are small parts of antigens (viruses, for example), with the potential to activate the immune response “, says Chacón. “Epitopes bind to cells and also to antibodies, a capacity that is used to develop serological diagnostic kits, which indicate the person’s exposure to the virus and new generation vaccines.”
Tests and vaccines
The researcher points out that, through biotechnological processes, it is possible to produce them on a large scale, safely and cheaply. “Currently, more than ten vaccines based on epitopes are being tested to combat covid-19”, he highlights. “Among them is EpiVacCorona, developed in Russia, whose tests are currently in clinical phases 1 and 2”, he highlights. These phases correspond to studies with healthy people and people with the disease, in small groups (20 to 100 people). At the moment, the most advanced vaccines, such as the one developed in the United Kingdom by the University of Oxford, are in phase 3 (study with larger groups, of up to 10,000 people, in different regions of the world).
According to Chacón, HLA genes are highly variable, with more than 22,000 types known in the human species, and their composition in each population is different. “Each type of HLA has an affinity for certain epitopes,” he says. “Thus, knowing the most frequent alleles in people in a region also allows predicting and knowing which are the best epitopes that could generate a more efficient immune response in these people.”
The research identified epitopes that would be able to be recognized by 100% of the most common types of HLA genes in South America. “They can be used for the development of diagnostic kits and epitopic vaccines against covid-19 specific to the region” , Chacón notes to USP’s Journal.
“The results of the work may help other studies that have been conducted to better understand the relationship between HLA genes and susceptibility to covid-19, explain why some people have lesser or greater severity of the disease.”
The genetic information gathered by the study may also contribute to research on infectious diseases, in addition to endemic, autoimmune diseases and cancer. “It is already known that the type of HLA can influence the person’s response to these diseases”, concludes the researcher.
The research was carried out by David Requena, from The Rockefeller University (United States), Aldhair Médico, from Universidad Peruana Cayetano Heredia (Peru), Ruy Diego Chacón, Manuel Ramírez and Obert Marín-Sánchez, from Universidad Nacional Mayor de San Marcos (Peru ).
The results of the work are described in the article Identification of Novel Candidate Epitopes on SARS-CoV-2 Proteins for South America: A Review of HLA Frequencies by Country, published on the website of the magazine Frontiers in Immunology on September 3.