HLA Class II Genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 Are Associated With the Antibody Response to Inactivated Japanese Encephalitis Vaccine

Aim: The objective of this study was to evaluate the association of the human leukocyte antigen (HLA) class II genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 with the humoral immune response elicited by inactivated Japanese encephalitis (JE) vaccine (IJEV). Methods: A total of 373 individuals aged 3–12 years in the Inner Mongolia Autonomous Region in China, who received two doses of IJEV at 0 and 7 days, were enrolled in the current study. Based on the individuals' specific JE virus (JEV)-neutralizing antibodies (NAbs), they were divided into a seropositive and a seronegative group. HLA-DRB1, HLA-DPB1, and HLA-DQB1 were genotyped using a sequencing-based typing method. Next, the association of the HLA class II genes and their haplotypes with antibody response was evaluated. Results: Based on NAbs, a total of 161 individuals were classified as seropositive and 212 as seronegative. DQB1(*)02:01 was significantly associated with JEV seropositivity (P < 0.001, OR = 0.364, 95% CI: 0.221–0.600), while DQB1(*)02:02 was significantly associated with JEV seronegativity (P = 5.03 × 10(−6), OR = 7.341, 95% CI: 2.876–18.736). The haplotypes DRB1(*)07:01-DPB1(*)04:01-DQB1(*) 02:01, DRB1(*)15:01-DPB1(*)02:01-DQB1(*)06:02, DRB1(*)07:01-DQB1(*)02:01, and DPB1(*)02:01-DQB1(*)06:02 were very frequent in the seropositive group, while DRB1(*)07:01-DPB1(*)17:01-DQB1(*)02:02, DRB1(*)07:01-DQB1(*)02:02, and DPB1(*)17:01-DQB1(*)02:02 were very frequent in the seronegative group. The presence of DRB1(*)01:01, DRB1(*)04:05, DRB1(*)09:01, DRB1(*)12:02, DRB1(*)13:02, and DRB1(*)14:01 was associated with a higher geometric mean titer (GMT) of NAbs than that of DRB1(*)11:01 at the DRB1 locus (P < 0.05). At the DPB1 locus, the presence of DPB1(*)05:01 was associated with higher GMTs than that of DPB1(*)02:01 and DPB1(*)13:01 (P < 0.05), and the presence of DPB1(*)04:01 and DPB1(*)09:01 was associated with higher GMTs than that of DPB1(*)13:01 (P < 0.05). Conclusions: The present study suggests that HLA class II genes may influence the antibody response to IJEV.