Peripheral Merozoite Surface Proteins Are Targets of Naturally Acquired Immunity against Malaria in both India and Ghana

Abstract

Development of a successful blood-stage vaccine against Plasmodium falciparum malaria remains a high priority. Immune-epidemiological studies are effective tools for the identification of antigenic-targets of naturally acquired immunity (NAI) against malaria. However, differences in study design and methodology may compromise inter-study comparisons. Here, we assessed antibody responses against intact merozoites and a panel of 24 recombinant merozoite antigens in longitudinal cohort studies of Ghanaian (n = 115) and Indian (n=121) populations using the same reagents and statistical methods. Anti-merozoites antibodies were associated with NAI in both the Indian (hazard ratio [lsqb]HR[rsqb] = 0.41, p = 0.020) and the Ghanaian (HR = 0.17, p < 0.001) participants. Of the 24 antigen-specific antibodies quantified, 12 and 8 were found to be protective in India and Ghana, respectively. Using LASSO regression, a powerful variable sub-selection technique, we identified subsets of four (MSP6, MSP3.7, MSPDBL2, and Pf12) and five (cMSP33D7, MSP3.3, MSPDBL1, GLURP-R2, and RALP-1) antigens which explained NAI better than the individual antibodies in India (HR=0.18, p< 0.001) and Ghana (HR=0.31, p< 0.001), respectively. IgG1 and/or IgG3 subclasses against five antigens from these subsets were associated with protection. Through this comparative study, maintaining uniformity of reagents and methodology, we demonstrate that NAI across diverse geographic regions may result from antibodies to multiple antigenic targets which constitute the peripheral merozoite surface protein complexes.