The appearance and fast spread of five SARS-CoV-2 variants (D614G, B.1.1.7-UK [^I+/-], B.1.351-South Africa [^I^2], P.1-Brazil [^I^3], B.167.2-India [^I']) have raised concerns regarding adaptive immunity, namely the extent to which antibodies against the original SARS-CoV-2 spike glycoprotein (S^natural) would protect against those variants. A related issue is how effective current vaccines are against the known variants of concern. This issue is important because all current vaccines have S^natural as their target antigen. The first step in initiating antibody production is the formation of a complex between an epitope of the foreign antigen (here, a spike glycoprotein) and a Human Leukocyte AntigenHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant. Class II molecule; this complex engages CD4+ T-lymphocytes for the initiation of antibody production by B cells (Major Histocompatibility Complex [MHC] restriction). Given the underlying mechanisms of long-term adaptive immunity, vaccines containing epitopes shared by all 6 spike glycoprotein variants and with high binding affinity to HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant. Class II molecules could potentially be good candidates for offering a universal protection against SARS-Cov-2. Numerous efforts have been made in determining vaccine targets for SARS-CoV-2 using computational methods. These methods are based on B cell and T cell epitope prediction and indeed extend beyond SARS-CoV-2 to encompass prediction of the pathogen-based immune response more generically. In the current study, we explored this approach by investigating in silico the binding affinities of all linear 15-, 18- and 22-amino acid long epitopes of S^natural and its 5 variants (S^D614G, S^B.1.1.7, S^B.1.351, S^P.1, S^P.167.2) to 66 common HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant. Class II alleles with global frequencies of ^ao/ooyen 0.01. We identified 18 such epitopes which occur in all 6 spike glycoproteins and which bind with very high affinity to HLAHuman Leukocyte Antigen (HLA)Genes that are located in the Major Histocompatibility Complex (MHC) of chromosome 6 and play a central role in immune recognition. Most investigations of association of HLA to various diseases have focused on evaluating HLA allele frequencies in diseases of interest, as compared to the general, healthy population. Such studies have demonstrated HLA involvement with cancer, autoimmune, and in- fectious diseases. HLA Class I proteins (HLA-A, B, C) are expressed on all nucleated cells and present peptides from endogenous proteins to cytotoxic T lymphocytes engaged in immune surveillance. HLA Class II proteins (HLA-DRB1, DRB3/4/5, DQB1, DPB1) are expressed on antigen-presenting cells and present peptides derived from exogenous proteins to CD4+helper T cells. A previous study of Gulf War syndrome in 27 veterans found that HLA DRB1*15 was more prevalent in cases than controls with an odds ratio of 1.66, although this association was not statistically significant. Class II molecules. Most of these molecules came from the DPB1 gene. The suitability of these candidate epitopes for a successful multivariant SARS-CoV-2 vaccine design remains to be determined.