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

Abstract

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.

Keywords: HLA class II genes; HLA-DM; antibody immune response; haplotype; inactivated Japanese encephalitis virus vaccine.