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. 2022 Aug 29:13:932043.
doi: 10.3389/fgene.2022.932043. eCollection 2022.

GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine

Ieva Čiučiulkaitė  1 , Birte Möhlendick  1 , Laura Thümmler  2 , Neslinur Fisenkci  2 , Carina Elsner  3 , Ulf Dittmer  3 , Winfried Siffert  1 , Monika Lindemann  2
Affiliations

GNB3 c.825c>T polymorphism influences T-cell but not antibody response following vaccination with the mRNA-1273 vaccine

Ieva Čiučiulkaitė et al. Front Genet. .

Abstract

Background: Immune responses following vaccination against COVID-19 with different vaccines and the waning of immunity vary 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 the SARS-CoV-2 spike protein and T-cell responses against a peptide pool of SARS-CoV-2 S1 proteins were measured 1 and 6 months after the second vaccination with mRNA-1273 in the main study group of 204 participants. Additionally, antibodies against the SARS-CoV-2 spike protein were measured in a group of 597 participants 1 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 the S1-peptide pool were significantly decreased from months 1 to 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 an 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 better T-cell-mediated protection against COVID-19 after vaccination with mRNA-1273.

Keywords: COVID-19; ELISpot; GNB3 c.825C>T; SARS-CoV-2; SARS-CoV-2 spike antibody titer; antigen-specific T-cell response; mRNA-1273.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Humoral and cellular immune responses were stratified by GNB3 genotypes 1 and 6 months after the second vaccination with mRNA-1273. Distribution of antibody concentrations against SARS-CoV-2 S1-RBD 1 month (A) and 6 months (B) after the second vaccination. ELISpot responses to the S1-protein of SARS-CoV-2 at 1 month (C) and 6 months (D) after the second vaccination. Antibody titers are reported in BAU/ml and T-cell response as spots increment. Red dashed lines indicate the cut-off for positivity (1.5 spots increment per 250,000 peripheral blood mononuclear cells).
FIGURE 2
FIGURE 2
Humoral (A) and cellular (B) immune response 1 and 6 months after the second vaccination with mRNA-1273 in the group of 64 participants who were available at both time points. Antibody titers are reported in BAU/ml and T-cell response as spots increment. Red dashed lines indicate the cut-off for positivity (1.5 spots increment per 250,000 peripheral blood mononuclear cells).
FIGURE 3
FIGURE 3
Comparison of humoral response and GNB3 genotypes 1 month after the second vaccination with mRNA-1273 in the replication group. The median of anti-spike antibody levels is given in BAU/ml.
See this image and copyright information in PMC

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