Research published this week in PLoS Medicine synthesizes information from many different studies that attempt to link specific antibody responses to Plasmodium falciparum with protection from clinical malaria and comes to important conclusions about which antigens might be worth advancing as vaccine candidates.
Malaria is a major global health problem. P. falciparum is the major cause and kills about one million people every year, mainly young children. However, immune responses to malaria are poorly understood, which has hindered the development of a vaccine against malaria. Antibody responses to proteins (antigens) produced by the merozoite life stage of malaria might protect against subsequent malaria infection. Therefore studying these antibody responses could be useful for identifying antigens to incorporate into vaccines against malaria.
Numerous studies have been performed on human antibody responses to P. falciparum merozoite antigens, but they have given conflicting results. Freya Fowkes and colleagues have completed a systematic review with meta-analysis for the first time of immune responses to P. falciparum. This study confirms that merozoite antigens are important targets of protective immunity in people and identifies specific antigens that could be prioritized for vaccine development. Specifically, in people with antibodies to the merozoite proteins MSP-3 and MSP-119, the risk of developing P. falciparum malaria was reduced by 54% and 18%, respectively, compared to people without antibodies to these antigens. Antibodies to other antigens, such as AMA1 were also linked with substantial protection from malaria.
The authors recommend that new prospective cohort studies are urgently needed to guide vaccine development. These studies must include a larger number of lead antigens and populations outside Africa.
Funding: This work was funded by the National Health and Medical Research Council of Australia (NHMRC, http://www.nhmrc.gov.au) project grant #516756, NHMRC IRIISS grant #361646 and the Victorian State Government Operational Infrastructure Support grant. JGB is supported by a Clinical Career Development Award, and JSR by a Medical Postgraduate Research Scholarship from the NHMRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Citation: Fowkes FJI, Richards JS, Simpson JA, Beeson JG (2010) The Relationship between Anti-merozoite Antibodies and Incidence of Plasmodium falciparum
Malaria: A Systematic Review and Meta-analysis. PLoS Med 7(1): e1000218. doi:10.1371/journal.pmed.1000218
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Freya Fowkes and James Beeson
Walter and Eliza Hall Institute of Medical Research
Infection and Immunity
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