Identification of HLA-A24:02-Restricted CTL Candidate Epitopes Derived from the Nonstructural Polyprotein 1a of SARS-CoV-2 and Analysis of Their Conservation Using the Mutation Database of SARS-CoV-2 Variants

• Published in: Microbiology spectrum Vol. 9; no. 3; p. e0165921
• Main Authors: Takagi, Akira, Matsui, Masanori
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 22.12.2021
• Subjects: Amino Acid Sequence; Animals; Antibodies, Neutralizing - immunology; CD8-Positive T-Lymphocytes - immunology; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 - virology; COVID-19 Vaccines - immunology; CTL epitope; Epitopes - genetics; Epitopes - immunology; HLA-A24 Antigen - genetics; HLA-A24 Antigen - immunology; HLA-A24 Antigen - isolation & purification; HLA-A24:02; Humans; Immunology; Mice; Mutation; Polyproteins - genetics; pp1a; Research Article; SARS-CoV-2; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology; T-Lymphocytes, Cytotoxic - immunology; vaccine; COVID-19; SARS-CoV-2; vaccine; pp1a; CTL epitope; HLA-A24:02; conserved epitope; variants
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/Spectrum.01659-21

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. 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.