Predicted Epitope Abundance Supports Vaccine-Induced Cytotoxic Protection Against SARS-CoV-2 Variants of Concern

Abstract

The effect of emerging SARS-CoV-2 variants on vaccine efficacy is of critical importance. In this study, the potential impact of mutations that facilitate escape from the cytotoxic cellular immune response in these new virus variants for the 551 most abundant HLA class I alleles was analyzed. Computational prediction showed that most of these alleles, that cover >90% of the population, contain enough epitopes without escape mutations in the principal SARS-CoV-2 variants. These data suggest that the cytotoxic cellular immune protection elicited by vaccination is not greatly affected by emerging SARS-CoV-2 variants.

Prediction of Conserved HLA Class I and Class II Epitopes from SARS-CoV-2 Licensed Vaccines Supports T-Cell Cross-Protection against SARS-CoV-1

“…Therefore, first bioinformatics prediction to the theoretical epitopes from the SARS-CoV-2 spike protein, the viral protein included in internationally licensed vaccines, was carried out as previously described [ 15 , 16 ]. Each of the 551 HLA class I alleles associated with the twelve canonical HLA-A and -B class I supertypes were analyzed, respectively ( Figure 1 ).…”

Predicted HLA Class I and Class II Epitopes From Licensed Vaccines Are Largely Conserved in New SARS-CoV-2 Omicron Variant of Concern

“…In the real scenario analyzed in the current study, the 30 changes, 3 deletions, and 1 insertion generated by the Omicron variant of concern versus current SARS-CoV-2 vaccines, only with the A03 supertype was a similar (26%) escape mutation rate found. A02 was the second supertype affected (21%), while in the other 10 HLA class I supertypes, this rate was less than 20%, resulting in a 12% escape mutation rate on average for the 12 HLA class I supertypes analyzed, less than half of the theoretical rate calculated by random mutation (12). B58, with only 2% altered epitopes, and B08 without predicted epitopes modified in Omicron strain versus SARS-CoV-2 vaccines were the HLA class I supertypes least impacted by the Omicron variant of concern.…”

“…In our previous study about the effect of emerging SARS-CoV-2 variants identified to May 2021 on cytotoxic T-cell response generated by the licensed vaccines, a prediction of the number of intact epitopes for some representative alleles of the twelve HLA class I supertypes was calculated after random progressive position sets ranging from the length of the full spike protein (12). In this hypothetical scenario, 39 random mutations in the spike protein sequence did not prevent the fact that the 75% of predicted cytotoxic epitopes derived from SARS-CoV-2 vaccines remained unaltered (12). In the real scenario analyzed in the current study, the 30 changes, 3 deletions, and 1 insertion generated by the Omicron variant of concern versus current SARS-CoV-2 vaccines, only with the A03 supertype was a similar (26%) escape mutation rate found.…”

“…Therefore, most HLA class I-and II-restricted peptides remain preserved. In addition, in the hypothetical scenario using random progressive mutation on SARS-CoV-2 spike protein previously described (12), an average of 81 mutations were necessary to destroy half of the predicted CD8 + T-cell epitopes generated by vaccination and restricted by all HLA class I supertypes. Thus, taking into account the above, it is probable that the impact of 80 mutations in the spike protein screened by natural selection was far less disruptive than the hypothetical scenario, and still, most HLA class I-and II-restricted peptides of multiple HLA supertypes remain preserved.…”

A Subtractive Proteomics Approach for the Identification of Immunodominant Acinetobacter baumannii Vaccine Candidate Proteins

“…By using a subtractive approach, we identified 34 unique proteins via infected patient sera, in both membranous and secretome of A. baumannii. Majority of those proteins were not deeply analyzed with classical approaches or in silico and was somehow disregarded as potential vaccine candidate (e.g., B0V885 / ABAYE3068) [21,25,26]. Taking into consideration of structure, transmembrane properties, epitope regions and solubility of identified proteins, we further analyzed nine of them as potential recombinant vaccine candidate.…”