Asian Flush Gene Variant Enhances Cellular Immunogenicity of COVID-19 Vaccine: Prospective Observation in the Japanese General Population
Sudarma Bogahawaththa,
Megumi Hara,
Takuma Furukawa,
Chiharu Iwasaka,
Takeshi Sawada,
Goki Yamada,
Mikiko Tokiya,
Kyoko Kitagawa,
Yasunobu Miyake,
Mizuho Aoki Kido,
Yoshio Hirota,
Akiko Matsumoto
Affiliations
Sudarma Bogahawaththa
Laboratory of Biochemistry, Department of Applied Biochemistry and Food Science, Faculty of Agriculture, Saga University, Honjo, Saga 840-8502, Japan
Megumi Hara
Department of Preventive Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Takuma Furukawa
Department of Preventive Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Chiharu Iwasaka
Department of Preventive Medicine, Faculty of Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Takeshi Sawada
Department of Histology and Neuroanatomy, Faculty of Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Goki Yamada
United Graduate School of Agriculture, Kagoshima University, Kagoshima 890-0065, Japan
Mikiko Tokiya
Department of Social and Environmental Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Kyoko Kitagawa
Division of Ultrastructural Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan
Yasunobu Miyake
Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga 849-8501, Japan
Mizuho Aoki Kido
Department of Histology and Neuroanatomy, Faculty of Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
Yoshio Hirota
Clinical Epidemiology Research Center, SOUSEIKAI Medical Group (Medical Co., LTA), Fukuoka 813-0017, Japan
Akiko Matsumoto
Department of Social and Environmental Medicine, Saga University, Nabeshima, Saga 840-8501, Japan
We previously reported a reduced humoral immune response to the COVID-19 vaccines. Subsequently, we observed a lower susceptibility to COVID-19 in individuals carrying the ALDH2 rs671 variant through a web-based retrospective survey. Based on these findings, we hypothesized that rs671 variant was beneficial for cellular immunity against COVID-19. Using the IFN-γ enzyme-linked immunospot (ELISPOT) assay, we assessed cellular immunity before and after COVID-19 vaccination in two subcohorts of a previously reported cohort. Subcohort 1 (26 participants) had six repeated observations at baseline after one to three doses, whereas subcohort 2 (19 participants) had two observations before and after the third dose. ELISPOT counts at six months after the second dose increased from baseline in carriers of the rs671 variant but not in non-carriers. A positive effect of rs671 on ELISPOT counts was estimated using a mixed model (183 observations from 45 participants), including the random effect of subcohort, repeated measures, and fixed effects of vaccine type, age, sex, height, lifestyle, steroid use, and allergic disease. There was no association between ELISPOT counts and specific IgG levels, suggesting a limitation in estimating protective potential by humoral response. Our sequential observational studies suggest a beneficial effect of the rs671 variant in SARS-CoV-2 infection via enhanced cellular immune response, providing a potential basis for optimizing preventive measures and drug development.
