GWAS identifying HLA‐DPB1 gene variants associated with responsiveness to hepatitis B virus vaccination in Koreans: Independent association of HLA‐DPB1*04:02 possessing rs1042169 G ‐ rs9277355 C ‐ rs9277356 A

Abstract

Recently, HLA class II loci, including HLA-DPB1, have been reported to be associated with interindividual variance in the hepatitis B (HB) vaccine response. In this study, we investigated significant single nucleotide polymorphisms (SNPs) for anti-HBs antibody levels in 6867 healthy Koreans using a genome-wide association study (GWAS).In GWAS, the top 20 SNPs that showed significant association with anti-HBs levels (P < 1.0 × 10 −29 ) all resided in HLA-DPB1. Utilizing PCR sequencing, we verified the relationship of the top 3 most significant SNPs (rs1042169, rs9277355 and rs9277356) from the GWAS and genotypes of HLA-DPB1 with the HB vaccine response in Korean infants who received a scheduled vaccination. The DPB1*04:02 allele has G, C and A nucleotides for the 3SNP sites, and was significantly more frequent in responders than in nonresponders (10.9% vs 1.0%, P c = 0.018). DPB1*05:01 was significantly more frequent in nonresponders than in responders (49.0% vs 31.1%, P c = 0.018).In multivariate logistic regression, DPB1*04:02 showed a significant association with both vaccine response (P = 0.037, OR = 8.465) and high-titre response (P = 0.027, OR = 9.860). The haplotypes rs1042169 G -rs9277355 C -rs9277356 A showed a significant association with a high-titre response only (P = 0.002, OR = 2.941). In conclusion, DPB1*04:02 possessing rs1042169 G -rs9277355 C -rs9277356 A is an independent predictor of the HB vaccine response in Koreans. K E Y W O R D Shepatitis B virus, HLA-DPB1, Korean, vaccine response

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines

“…Ragone et al. found HLA did not impact on short-medium-term antibody response to Pfizer-BioNTech BNT162b2 vaccine, which was a SARS-CoV-2 mRNA vaccine ( 36 ), though HLA variants have been shown to be associated with antibody response to several other pathogen vaccines ( 15 – 18 , 37 – 39 ). Consistent of this research, we did not found associations between HLA variants and antibody response either.…”

“…Human genetic background has been suggested to contribute to inter-individual difference in antibody response to many vaccines ( 13 , 14 ). For example, multiple studies revealed HLA variants were associated with antibody response to hepatitis B vaccine ( 15 – 18 ). CD46 and IFI44L genetic variants were revealed to be associated with neutralizing antibody response to measles vaccine ( 19 ).…”

HLA-A*03:01 is associated with increased risk of fever, chills, and more severe reaction to Pfizer-BioNTech COVID-19 vaccination

“…However, to our knowledge, very few studies have been published reporting genetic associations with reactogenicity after non live-attenuated vaccines. In the past, a few studies have investigated the genetics of response to vaccines by looking at the levels of antibodies after a certain time period in vaccine recipients, often identifying associations with HLA genes 15,16 . Other studies have elucidated why some patients presented with a rare life-threatening disease following vaccinations with live-attenuated vaccines 17 .…”

Will Host Genetics Affect the Response to SARS-CoV-2 Vaccines? Historical Precedents

“…However, despite the continuously growing number of vaccine-associated GWASs, these studies are either clustered within specific ethnic groups, or focused on a limited number of pathogens. Most of the currently available reports are on vaccine response to hepatitis B, measles, rubella, influenza A, smallpox, anthrax, and mumps (4,5,7,(25)(26)(27)(28)(29).…”

“…The most significant associations were linked to HLA polymorphisms. Multiple HLA alleles were associated with anti-hepatitis surface antigen IgG levels including HLA-DPB1 and HLA-DRAB5 and HLA-DQA1 (5,(25)(26)(27). HLA genes are known to be the most polymorphic region of human genes, and encodes surface proteins which are essential in self and non-self-antigen presentation (37).…”