Predição e estudo das interações dos HLAs de classe I e II com as proteínas do vírus da febre amarela e do vírus vacinal YF-17DD

Abstract

Yellow fever (YF) is a febrile hemorrhagic disease caused by the yellow fever virus (YFV) and is responsible for 29,000 to 60,000 deaths annually. It is estimated that more than 700 million unvaccinated people live in areas at risk of infection, suggesting that YF has an extremely high potential to have an impact on population health and a financial burden on health systems. YF can be prevented through vaccination with the attenuated YF-17DD virus, which induces neutralizing antibodies associated with protective immunity against YF in 90 to 98% of vaccinated individuals. The percentage of 2 to 10% of YF vaccination failures is still not well understood. A possible reason for vaccination failures may be defective antigen presentation by the vaccinated Human Leukocyte Antigen (HLA) repertoires. Here, we hypothesize that cases of YF vaccine failure occur in individuals with HLA repertoires composed of alleles incapable of efficiently presenting YF-17DD antigens. To test our hypothesis, we used bioinformatics methods based on artificial neural networks to predict the interactions of the YF-17DD and YFV antigens most likely to bind to the HLA alleles studied here, and we used this information to create a score to classify the HLA alleles studied here. HLA alleles according to their ability to interact with YFV and YF-17DD epitopes. Subsequently, we used the score of each HLA allele to score the HLAs-I and HLAs-II repertoire of individuals immunized with the YF-17DD vaccine and correlated the scores of each individual's HLA repertoires with their ability to produce antibodies. neutralizing agents against YF-17DD 28 days after vaccination. We found that individuals with HLA repertoires with higher scores, that is, individuals with HLA repertoires composed of alleles that have a high capacity to interact with YF-17DD proteins, had higher anti-YF-17DD neutralizing antibody titers when compared with individuals who have low-scoring HLA repertoires. These findings suggest that the presence of HLAs with a high number of interactions with YF-17DD peptides in an individual's repertoire is related to their ability to produce neutralizing anti-YF-17DD antibodies, which would be correlated with protective immunity against YF.