Influence of HLA-DRB1 Alleles on Antibody Responses to PfCP-2.9-Immunized and Naturally Infected Individuals

Abstract

The Plasmodium falciparum chimeric protein, PfCP-2.9, which consists of apical membrane antigen (AMA)-1(III) and merozoite surface protein (MSP)1-19, is a promising asexual-stage malaria vaccine currently being evaluated in clinical trials. This study attempts to investigate the potential association between human leukocyte antigen (HLA)-DRB1 genotype and antibody response against PfCP-2.9 in healthy population and malaria patients. We investigated the HLA-DRB1 alleles in 40 participants from phase I trial and 86 malaria patients from southern China by polymerase chain reaction with allele sequence-specific primers. The antibody and cellular response against PfCP-2.9 or its components were measured by enzyme-linked immunosorbent assay and T lymphocyte proliferation assay. In clinical subjects, the anti-PfCP-2.9 antibody response was likely suppressed by HLA-DR6 alleles, which was consistent with the T lymphocyte proliferation assay. Nevertheless, HLA-DR7 positively correlated with antibody responses in naturally infected individuals while DR8 correlated with weaker antibody responses for all the three recombinant proteins. Moreover, parasitemia was significantly lower in samples with higher antibody levels against PfCP-2.9 or rMSP1-19, but not for rAMA-1(III). These data suggest that antibody responses against PfCP-2.9, AMA-1(III), or MSP1-19 elicited by vaccine formulation or natural infection are controlled by different HLA-II alleles. Moreover, the antibody response to MSP1-19 contributed more to protection immunity than AMA-1(III).