AUTHOR=Čiučiulkaitė Ieva , Möhlendick Birte , Thümmler Laura , Fisenkci Neslinur , Elsner Carina , Dittmer Ulf , Siffert Winfried , Lindemann Monika TITLE=GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine JOURNAL=Frontiers in Genetics VOLUME=Volume 13 - 2022 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.932043 DOI=10.3389/fgene.2022.932043 ISSN=1664-8021 ABSTRACT=Background: Immune responses following vaccination against COVID-19 with different vaccines and waning of immunity varies within the population. Genetic host factors are likely to contribute to this variability. However, to the best of our knowledge, no study on G protein polymorphisms and vaccination responses against COVID-19 has been published so far. Methods: Antibodies against SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured one and six months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against SARS-CoV-2 spike protein were measured in a group of 597 participants one month after the second vaccination with mRNA-1273. Genotypes of GNB3 c.825C>T were determined in all participants. Results: The median antibody titer against the SARS-CoV-2 spike protein and median values of spots increment in the SARS-CoV-2 IFN-γ ELISpot assay against S1-peptide pool was significantly decreased from month 1 to month 6 (P<0.0001). Genotypes of GNB3 c.825C>T had no influence on the humoral immune response. At month 1, CC genotype carriers had significantly increased T-cell responses compared to CT (P=0.005) or TT (P=0.02) genotypes. CC genotype carriers had an almost 6-fold increased probability compared to TT genotype carriers and almost 3-fold increased probability compared to T-allele carriers to mount a SARS-CoV-2-specific T-cell response above the median value. Conclusion: CC genotype carriers of the GNB3 c.825C>T polymorphism have an increased T cell immune response to SARS-CoV-2, which may indicate a better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.