Association of HLA-DM and HLA class II genes with antibody response induced by inactivated Japanese encephalitis vaccine

HLA class II molecules, HLA-DR, DP and DQ, together with HLA II-like protein DM, play a dominant role in the processing and presentation of antigens, which may influence vaccine effectiveness. We previously demonstrated that variations in the HLA-DRB1, DPB1 and DQB1 genes may affect the neutralising antibody (NAb) response induced by the inactivated Japanese encephalitis vaccine (IJEV). In the present study, we genotyped HLA-DPA1, DQA1, DMA and DMB genes and used previous HLA-DRB1, DPB1 and DQB1 data to evaluate the association of these genes with IJEV-induced NAbs, at both the seroconversion and geometric mean titres (GMTs). We confirmed the seropositive association of DQB1*02:01 and NAbs (0.156 vs. 0.075, p_adj = 0.018; OR = 2.270; 95% CI = 1.285-3.999) and seronegative association of DQB1*02:02 (0.014 vs. 0.09, p_adj = 0.0002; OR = 0.130; 95% CI = 0.047-0.400). Furthermore, the DMB*01:03-DMA*01:01-DPA1*01:03-DPB1*04:01 haplotype was associated with a negative response (0.020 vs. 0.074; p_adj = 0.03; OR = 0.250; 95% CI = 0.097-0.649), whereas DRB1*15:02-DMB*01:01-DMA*01:01 was associated with a positive response (0.034 vs. 0; p_adj = 0.044). In addition, DRB1*12:02, DRB1*13:02, DPB1*04:01, DPB1*05:01, DPB1*09:01, DQA1*06:01 and DQA1*01:02 were associated with a higher GMT of NAbs, whereas DRB1*11:01, DPB1*13:01 and DQA1*05:05 were associated with a lower GMT of NAbs. In conclusion, the present study suggests that variations in the HLA-DM and HLA class II genes, as well as their combined allotypes, may influence the IJEV NAbs at seroconversion and GMT levels.

Automated summary

This study found that variations in the HLA-DM and HLA class II genes may influence the expression of neutralising antibodies (NAbs) induced by the inactivated Japanese encephalitis vaccine (IJEV) at both the seroconversion and geometric mean titres (GMT) levels. DQB1*02:01 was positively associated with NAbs, while DQB1*02:02 was negatively associated. Additionally, different haplotypes were associated with the expression levels of NAbs.