Single Nucleotide Polymorphisms in the Human Leukocyte Antigen Region Are Associated With Hemagglutination Inhibition Antibody Response to Influenza Vaccine.

Shuyi Zhong,Mao Li,Dayan Wang,Simin Wen,Yanhui Cheng,Yuelong Shu,Hejiang Wei

doi:10.3389/fgene.2022.790914

Abstract

Background: The annual death associated with seasonal influenza is 290,000–650,000 globally, which can be effectively reduced by influenza vaccination. However, the protective hemagglutination inhibition (HAI) antibody response to influenza vaccine is affected by many factors, among which single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can alter the antigen-presenting function of the HLA molecule, thus influencing the process of antibody mounting against vaccine antigen. Methods: Healthy subjects of the Han nationality were recruited and received seasonal trivalent influenza vaccine. Paired serum samples collected on and approximately 28 days after vaccination were tested in parallel by HAI assays. HLA alleles related to the immune response to influenza vaccine reported in the previous literature were summarized, and six corresponding tag SNPs were selected and genotyped using the MassARRAY technology platform. Results: The effects of HLA SNPs on HAI antibody response to influenza vaccine varied with different vaccine antigens. The AA genotype of rs41547618 was correlated with low A/H1N1-specific antibody titer compared with the GG + GA genotype (p = .007). The TT genotype of rs17885382 was correlated with low A/H3N2-specific antibody titer compared with the CC + CT genotype (p = .003). In addition, haplotype consisting of rs41542812—rs17885382—rs2068205—rs41547618—rs6905837—rs9270299—CCTGCA was correlated with non-responsiveness to influenza vaccine (OR = 2.39, 95% CI = 1.02–5.62). Conclusion: HLA SNPs were associated with HAI antibody response to influenza vaccine, which can help in a better understanding of the varied responsiveness to influenza vaccine in the population.

Highlights

Influenza remains one of the main threats to public health worldwide, resulting in seasonal epidemics with 290–650 thousand deaths annually (Iuliano et al, 2018)
Influenza vaccines that were used for adults contained 15 μg hemagglutination (HA) for each strain and were composed as recommended by the World Health Organization (WHO) for the northern hemisphere, details of which can be found in Supplementary Table S1
All the same among the three genotype carriers of rs41547618 (p = .006), and AA genotype correlated with low A/H1N1-specific antibody titer compared with the GG + GA genotype (p = .007), which was still significant after the Bonferroni correction

Summary

Introduction

Influenza remains one of the main threats to public health worldwide, resulting in seasonal epidemics with 290–650 thousand deaths annually (Iuliano et al, 2018). The immune response to influenza vaccine may be influenced by hostrelated factors such as age, gender, health condition, and genetic variants (Powers and Belshe, 1993; Castrucci, 2018; Scepanovic et al, 2018). Single nucleotide polymorphisms (SNPs) may change the binding region of HLA molecular peptides, affecting its role in the presentation of the influenza vaccine antigen. The protective hemagglutination inhibition (HAI) antibody response to influenza vaccine is affected by many factors, among which single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can alter the antigen-presenting function of the HLA molecule, influencing the process of antibody mounting against vaccine antigen

Methods

Results

Conclusion