Polymorphism of the <scp>HLA</scp> system and weak antibody response to <scp>BNT162b2 mRNA</scp> vaccine

Crocchiolo, Roberto; Gallina, Anna Maria; Pani, Arianna; Campisi, Daniela; Cento, Valeria; Sacchi, Nicoletta; Miotti, Valeria; Gagliardi, Oscar Matteo; D’Amico, Federico; Vismara, Chiara; Cornacchini, Giorgia; Lando, Giuliana; Cuppari, Irene; Scaglione, Francesco; Rossini, Silvano

doi:10.1111/tan.14546

Cited by 19 publications

(35 citation statements)

References 27 publications

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“…This study found that HLA-A*03:01 frequency was decreased in weaker antibody responder after vaccination while frequencies of the alleles A*33:03, B* 58:01 were increased and thus associated with a weak humoral response. 50 The results of these last two studies are congruent with those from our study. Indeed, even in our cohort, A*03:01 is associated with a more efficient antibody response and DRB1*15:01 with a cellular response.…”

Section: Discussionsupporting

confidence: 90%

The humoral and cellular response tomRNA SARS‐CoV‐2 vaccine is influenced byHLApolymorphisms

Bertinetto

Mapelli

Mazzola

et al. 2023

HLA

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Host genetic variability contributes to susceptibility to SARS‐CoV‐2 infection and COVID‐19 evolution and the role of HLA system has not clearly emerged, suggesting the involvement of other factors. Studying response to vaccination with Spyke protein mRNA represents an ideal model to highlight whether the humoral or cellular responses are influenced by HLA. Four hundred and sixteen workers, vaccinated with Comirnaty beginning 2021, were selected within the Azienda Ospedaliera Universitaria “Città della Salute e della Scienza di Torino.” The humoral response was determined with the LIAISON® kit, while the analysis of the cellular response was performed with the Quantiferon SARS‐CoV‐2 assay, for the S1 (receptor‐binding domain; Ag1) and S1 and S2 (Ag2) subunits of the Spyke protein. Six HLA loci were typed by next‐generation sequencing. Associations between HLA and vaccine response were performed with univariate and multivariate analyses. An association was found between A*03:01, B*40:02 and DPB1*06:01 and high antibody concentration and between A*24:02, B*08:01 and C*07:01 and low humoral responses. The haplotype HLA‐A*01:01 ~ B1*08:01 ~ C*07:01 ~ DRB1*03:01 ~ DQB1*02:01 conferred an increased risk of low humoral response. Considering cellular responses, 50% of the vaccinated subjects responded against Ag1 and 59% against Ag2. Carriers of DRB1*15:01 displayed a higher cellular response both to Ag1 and Ag2 compared to the rest of the cohort. Similarly, DRB1*13:02 predisposed to a robust cellular response to Ag1 and Ag2, while DRB1*11:04 showed an opposite trend. Cellular and humoral responses to Comirnaty are influenced by HLA. Humoral response is mainly associated to class I alleles, with A*03:01, previously associated to protection against severe COVID‐19, and response to vaccination, standing out. Cellular response predominantly involves class II alleles, with DRB1*15:01 and DPB1*13:01 prevailing. Affinity analysis for Spyke peptides is generally in line with the association results.

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Section: Discussionsupporting

confidence: 90%

The humoral and cellular response tomRNA SARS‐CoV‐2 vaccine is influenced byHLApolymorphisms

Bertinetto

Mapelli

Mazzola

et al. 2023

HLA

View full text Add to dashboard Cite

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“…Common factors such as age, sex, pre-existing conditions, or immunosuppressive therapy have been investigated and shown to contribute to this variability ( Geisen et al, 2021 ; Lindemann et al, 2021 ; Simon et al, 2021 ; Steensels et al, 2021 ; Widge et al, 2021 ). In addition, genetic host factors are also likely to contribute to this variability ( Crocchiolo et al, 2022 ; Gutierrez-Bautista et al, 2022 ). However, to the best of our knowledge, no studies on vaccination against COVID-19 and G protein polymorphisms have been published so far.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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“…Although recent studies suggested that HLA polymorphisms might unlikely account for the wide disparities in COVID-19 prognosis, they concluded on the potential role of HLA polymorphisms on the development of SARS-CoV-2 immunity also after vaccination by evaluating the association between specific HLA variants and vaccine response ( Copley et al, 2021 ; Shukla et al, 2022 ). Even though a first extensive report excluded the HLA impact on the immunoglobulin level fluctuation and duration ( Ragone et al, 2021 ), particular attention has been later directed toward a selected locus ( HLA-A*03:01 ) associated to a weak antibody response and negative side effects after Pfizer–BioNTech vaccine ( Bolze et al, 2022 ; Crocchiolo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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 (r2 = 0.807; p < 0.0001) and was confirmed during the first 90 days (T1) after vaccination (r2 = 0.789; p = 0.0001) and 91–190 days (T2) after vaccination (r2 = 0.764; p = 0.0001) for both vaccine types (r2 = 0.842; p = 0.0001 and r2 = 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.

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Polymorphism of the HLA system and weak antibody response to BNT162b2 mRNA vaccine

Cited by 19 publications

References 27 publications

The humoral and cellular response tomRNA SARS‐CoV‐2 vaccine is influenced byHLApolymorphisms

The humoral and cellular response tomRNA SARS‐CoV‐2 vaccine is influenced byHLApolymorphisms

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

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

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