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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.

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