ABSTRACT COVID-19 vaccines are currently being administered worldwide and playing a critical role in controlling the pandemic. They have been designed to elicit neutralizing antibodies against Spike protein of the original SARS-CoV-2, and hence they are less effective against SARS-CoV-2 variants with mutated Spike than the original virus. It is possible that novel variants with abilities of enhanced transmissibility and/or immunoevasion will appear in the near future and perfectly escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8 + cytotoxic T lymphocytes (CTLs). Several lines of evidence suggest the contribution of CTLs on the viral control in COVID-19, and CTLs target a wide range of proteins involving comparatively conserved nonstructural proteins. Here, we identified 22 HLA-A*24:02-restricted CTL candidate epitopes derived from the nonstructural polyprotein 1a (pp1a) of SARS-CoV-2 using computational algorithms, HLA-A*24:02 transgenic mice and the peptide-encapsulated liposomes. We focused on pp1a and HLA-A*24:02 because pp1a is relatively conserved and HLA-A*24:02 is predominant in East Asians such as Japanese. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by a number of mutations in the Sequence Read Archive database of SARS-CoV-2 variants. The information of such conserved epitopes might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any SARS-CoV-2 variants by the induction of both anti-Spike neutralizing antibodies and CTLs specific for conserved epitopes. IMPORTANCE COVID-19 vaccines have been designed to elicit neutralizing antibodies against the Spike protein of the original SARS-CoV-2, and hence they are less effective against variants. It is possible that novel variants will appear and escape from vaccine-elicited immunity. Therefore, the current vaccines may need to be improved to compensate for the viral evolution. For this purpose, it may be beneficial to take advantage of CD8 + cytotoxic T lymphocytes (CTLs). Here, we identified 22 HLA-A*24:02-restricted CTL candidate epitopes derived from the nonstructural polyprotein 1a (pp1a) of SARS-CoV-2. We focused on pp1a and HLA-A*24:02 because pp1a is conserved and HLA-A*24:02 is predominant in East Asians. The conservation analysis revealed that the amino acid sequences of 7 out of the 22 epitopes were hardly affected by mutations in the database of SARS-CoV-2 variants. The information might be useful for designing the next-generation COVID-19 vaccine that is universally effective against any variants.
【저자키워드】 COVID-19, SARS-CoV-2, Vaccine, variants, CTL epitope, HLA-A*24:02, pp1a, conserved epitope, 【초록키워드】 neutralizing antibody, COVID-19 vaccine, pandemic, Mutation, Lymphocytes, Immunity, Neutralizing antibodies, spike, variant, SARS-CoV-2 variant, virus, CD8, database, variants, Spike protein, Protein, nonstructural proteins, Epitopes, Viral, Transmissibility, SARS-CoV-2 variants, viral evolution, Japanese, HLA-A*24:02, pp1a, information, epitope, Critical, CTL, Amino acid, Evidence, cytotoxic T lymphocytes, Analysis, East Asians, CTLs, amino acid sequence, HLA-A, Algorithms, Amino acid sequences, transgenic mice, viral control, polyprotein, cytotoxic T lymphocyte, Administered, Sequence Read Archive, effective, affected, conserved, less, elicit, mutated, predominant, the Spike, East Asian, 【제목키워드】 conservation, CTL, identification, candidate,