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

摘要

>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.