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. 2022 Nov 30:13:1028081.
doi: 10.3389/fgene.2022.1028081. eCollection 2022.

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

Donato Gemmati  1   2   3 , Giovanna Longo  1   2 , Ines Gallo  1   2 , Juliana Araujo Silva  1   2 , Paola Secchiero  1 , Giorgio Zauli  4 , Stefania Hanau  5 , Angelina Passaro  1 , Patrizia Pellegatti  6 , Stefano Pizzicotti  6 , Maria Luisa Serino  2 , Ajay Vikram Singh  7 , Veronica Tisato  1   3
Affiliations

Host genetics impact on SARS-CoV-2 vaccine-induced immunoglobulin levels and dynamics: The role of TP53, ABO, APOE, ACE2, HLA-A, and CRP genes

Donato Gemmati et al. Front Genet. .

Abstract

Background: Development and worldwide availability of safe and effective vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to fight severe symptoms of coronavirus disease 2019 (COVID-19) and block the pandemic have been a great achievement and stimulated researchers on understanding the efficacy and duration of different vaccine types. Methods: We investigated the levels of anti-SARS-CoV-2 antibodies (IgG) and neutralizing antibodies (NAbs) in 195 healthy adult subjects belonging to the staff of the University-Hospital of Ferrara (Italy) starting from 15 days up to 190 days (about 6 months) after the second dose of the BNT162b2 (Pfizer-BioNTech) mRNA-based vaccine (n = 128) or ChAdOx1 (AstraZeneca) adenovirus-based vaccine (n = 67) using a combined approach of serological and genomics investigations. Results: A strong correlation between IgG and NAb levels was detected during the 190 days of follow-up (r 2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r 2 = 0.789; p = 0.0001) and 91-190 days (T2) after vaccination (r 2 = 0.764; p = 0.0001) for both vaccine types (r 2 = 0.842; p = 0.0001 and r 2 = 0.780; p = 0.0001 for mRNA- and adenovirus-based vaccine, respectively). In addition to age (p < 0.01), sex (p = 0.03), and type of vaccine (p < 0.0001), which partially accounted for the remarkable individual differences observed in the antibody levels and dynamics, interesting genetic determinants appeared as significant modifiers of both IgG and NAb responses among the selected genes investigated (TP53, rs1042522; APOE, rs7412/rs429358; ABO, rs657152; ACE2, rs2285666; HLA-A rs2571381/rs2499; CRP, rs2808635/rs876538; LZTFL1, rs35044562; OAS3, rs10735079; SLC6A20, rs11385942; CFH, rs1061170; and ACE1, ins/del, rs4646994). In detail, regression analysis and mean antibody level comparison yielded appreciable differences after genotype stratification (P1 and P2, respectively, for IgG and NAb distribution) in the whole cohort and/or in the mRNA-based vaccine in the following genes: TP53, rs1042522 (P1 = 0.03; P2 = 0.04); ABO, rs657152 (P1 = 0.01; P2 = 0.03); APOE, rs7412/rs429358 (P1 = 0.0018; P2 = 0.0002); ACE2, rs2285666 (P1 = 0.014; P2 = 0.009); HLA-A, rs2571381/rs2499 (P1 = 0.02; P2 = 0.03); and CRP, rs2808635/rs876538 (P1 = 0.01 and P2 = 0.09). Conclusion: High- or low-responsive subjects can be identified among healthy adult vaccinated subjects after targeted genetic screening. This suggests that favorable genetic backgrounds may support the progression of an effective vaccine-induced immune response, though no definite conclusions can be drawn on the real effectiveness ascribed to a specific vaccine or to the different extent of a genotype-driven humoral response. The interplay between data from the polygenic predictive markers and serological screening stratified by demogeographic information can help to recognize the individual humoral response, accounting for ethnic and geographical differences, in both COVID-19 and anti-SARS-CoV-2 vaccinations.

Keywords: BNT162b2 (Pfizer–BioNTech); COVID-19; COVIDomics; ChAdOx1 (AstraZeneca); SARS-CoV-2; SNPs; vaccine; vaccine pharmacogenomics.

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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
Scatter plots of the distribution of antibody levels after second dose of vaccine. (A,B) IgG and NAbs kinetic distributions in the whole cohort of subjects. (C,D) IgG and NAbs distribution stratified by the vaccine type (mRNA-based vaccine: blue dots/line and vector-based vaccine: red dots/line). (E,F) IgG and NAbs distribution, respectively, stratified by T1 and T2 recruitment time (T1: blue dots/line and T2: red dots/line). Each panel shows the specific regression line and the r-coefficient.
FIGURE 2
FIGURE 2
IgG and NAbs correlation analysis. (A) Correlation between IgG and NAbs level distributions in the whole cohort of subjects. (B) Correlation between IgG and NAbs stratified by T1 and T2 (T1: blue dots/line and T2: red dots/line). (C) Correlation between IgG and NAbs stratified by vaccine formulation (mRNA-based vaccine: blue dots/line and vector-based vaccine: red dots/line). Each panel shows the specific regression line and r-coefficient.
FIGURE 3
FIGURE 3
Scatter plots and regression analyses of IgG and NAbs levels stratified by the selected gene variants in the whole cohort. (A,C,E) IgG and (B,D,F) NAbs kinetics according to TP53 (rs1042522), ABO (rs657152), and APOE (rs7412/rs429358). Each panel shows the specific regression lines, according to the indicated genotype/haplotype.
FIGURE 4
FIGURE 4
Scatter plots and regression analyses of IgG and NAbs levels stratified by ACE2 (rs2285666) genotypes. (A,C) IgG and (B,D) NAbs kinetics in the whole cohort (A,B) and in the mRNA-based vaccine subgroup (C,D). Each panel shows the specific regression lines, according to the indicated genotype.
FIGURE 5
FIGURE 5
Scatter plots and regression analyses of IgG and NAbs levels stratified by HLA-A (rs2571381/rs2499). (A,C) IgG and (B,D) NAbs kinetics in the whole cohort (A,B) and in the mRNA-based vaccine subgroup (C,D). Each panel shows the specific regression lines according to the indicated haplotype.
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