Evaluation of specific antibody responses to selected malaria vaccine candidates in Zimbabwean children

Abstract

Introduction: There is high malaria related morbidity and mortality amongst infants and children in malaria endemic areas. An In-depth understanding of protective immunity correlates enables the long due necessary development of an effective malaria vaccine. This study aimed at evaluating antibody responses to apical membrane antigen 1 (AMA 1) that helps P falciparum entry into red blood cells, Glutamate rich protein (GLURP), an antigen expressed in the whole life cycle of the malaria causing pathogen, merozoite surface protein-1 (MSP 1) coding for a major antigen in the asexual stage of P falciparum and merozoite surface protein 3 (MSP 3), a polymorphic blood stage malaria antigen in Zimbabwean children living in malaria endemic areas.
Methods: We characterized humoral immune responses to malaria vaccine candidates in a two year longitudinal survey among 136 children (6-16 years) from Burma and Kariba in Zimbabwe. Blood samples were collected and analyzed for malaria parasites, plasma and antibody titers against malaria vaccine candidates [MSP1, MSP3, GLURP, AMA] by ELISA technique. The blood samples were also checked for potential confounders like anemia, bilharzia and HIV sero-status using the ELISA technique.
Results: Ig levels were significantly different (p < .0001) across the three time points, and against the different candidates (p < .0001). MSP3 had the highest (13,552.2) and GLURP the least (4,741.6) IgM titers. However, IgG, IgG1, IgG3 and IgG4 levels were highest against AMA compared to other vaccine candidates, [anti-MSP3 IgG3 (15.3) and anti-GLURP IgG4 (58.7)]. Anemia burden was about 44% at baseline with a threefold decrease (-16%) over the 12 month follow up.
Conclusions: This study highlights the need for robust evaluation of several malaria vaccine candidates in combination to understand correlates of protective immunity as suggested by the significant antibody levels against the four vaccine candidates. Longer follow up periods are needed to assess the impact of continuous malaria exposure on host immune responses. Multivalent malaria vaccine development offer a better chance towards an efficacious malaria vaccine compared to monovalent vaccine. Antibody levels against the four vaccine candidates were significant suggesting that an ideal malaria vaccine should target more than one antigen.