In this study, we examined the correlation between the frequency of allelic variants of the class II human leukocyte antigen (HLA) DR, DQ and DP gene loci and the quantitative humoral immune response observed in 71 Thai volunteers, subsequent to vaccination with a conjugated subunit vaccine. This vaccine was designed to induce antibodies directed against the immunodominant repeat region of the Plasmodium falciparum circumsporozoite (CS) protein. The presence of the DPB1*0501, a relatively common allele in Asian populations, was found to be associated with high vaccine‐induced CS repeat‐specific antibody responses in the volunteers. Given the increasing focus on the use of subunit vaccines in the control of infectious diseases, consideration of the influence of class II allele frequencies in ethnically diverse recipient populations may be important.