Abstract
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.
Highlights
Japanese encephalitis (JE) is one of the most serious mosquitoborne infectious diseases, with approximately 67,900 individuals being infected by the JE virus (JEV) annually [1]
The present study suggests that human leukocyte antigen (HLA) class II genes may influence the antibody response to inactivated JE vaccine (IJEV)
We examined the association of HLA class II genes with the IJEV antibody response to reveal the role of the genetic variation in the HLA class II genes in the IJEV immune response
Summary
Japanese encephalitis (JE) is one of the most serious mosquitoborne infectious diseases, with approximately 67,900 individuals being infected by the JE virus (JEV) annually [1]. 75% of these individuals are under 14 years of age, and 50% of the infections occur in China [2, 3]. Several studies have reported that the efficacy of attenuated JE vaccine has reached 85–99.26% in Chinese, South Korean, and Nepalese children; it exhibited only 67.2% efficacy in Indians after primary immunization [11,12,13,14]. These results indicate that different genetic backgrounds of hosts could play an important role in the efficacy of JE vaccines
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