Acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria
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Date
2016
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BioMed Central
Abstract
Background: Malaria still represents a major cause of morbidity and mortality predominantly in several developing
countries, and remains a priority in many public health programmes. Despite the enormous gains made in control
and prevention the development of an effective vaccine represents a persisting challenge. Although several para‑
site antigens including pre-erythrocytic antigens and blood stage antigens have been thoroughly investigated, the
identification of solid immune correlates of protection against infection by Plasmodium falciparum or clinical malaria
remains a major hurdle. In this study, an immuno-epidemiological survey was carried out between two populations
naturally exposed to P. falciparum malaria to determine the immune correlates of protection.
Methods: Plasma samples of immune adults from two countries (Ghana and Madagascar) were tested for their
reactivity against the merozoite surface proteins MSP1-19, MSP3 and AMA1 by ELISA. The antigens had been selected
on the basis of cumulative evidence of their role in anti-malarial immunity. Additionally, reactivity against crude P.
falciparum lysate was investigated. Purified IgG from these samples were furthermore tested in an invasion inhibition
assay for their antiparasitic activity.
Results: Significant intra- and inter- population variation of the reactivity of the samples to the tested antigens
were found, as well as a significant positive correlation between MSP1-19 reactivity and invasion inhibition (p < 0.05).
Interestingly, male donors showed a significantly higher antibody response to all tested antigens than their female
counterparts. In vitro invasion inhibition assays comparing the purified antibodies from the donors from Ghana and
Madagascar did not show any statistically significant difference. Although in vitro invasion inhibition increased with
breadth of antibody response, the increase was not statistically significant.
Conclusions: The findings support the fact that the development of semi-immunity to malaria is probably con‑
tingent on the development of antibodies to not only one, but a range of antigens and that invasion inhibition in
immune adults may be a function of antibodies to various antigens. This supports strategies of vaccination including
multicomponent vaccines as well as passive vaccination strategies with antibody cocktails.
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This article is published by BioMed Central.
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Citation
Addai‑Mensah et al. Malar J (2016) 15:65 DOI 10.1186/s12936-016-1112-1