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Merozoite surface protein-1 from is a major target of opsonizing antibodies in individuals with acquired immunity against malaria.

Clin Vaccine Immunol; 2017 Sep 06.
Article in English | MEDLINE | ID: mdl-28877929

Abstract

Naturally acquired immunity against malaria is largely mediated by serum antibodies controlling levels of blood stage parasites. A limited understanding of the antigenic targets and functional mechanisms of protective antibodies has hampered so far the development of efficient malaria vaccines. Besides directly inhibiting growth of parasites, antibodies can opsonize merozoites and recruit immune effector cells such as monocytes or neutrophils. Antibodies against the vaccine candidate merozoite surface protein-1 (MSP-1) are acquired during natural infection and have been associated with protection against malaria in several epidemiological studies.Here we analyzed serum antibodies from semi-immune individuals from Burkina Faso for their potential (i) to directly inhibit the growth of blood stages and (ii) to opsonize merozoites and induce antibody-dependent respiratory burst (ADRB) of neutrophils.While a few sera were identified, which directly inhibited growth of blood stages, IgG from all individuals clearly mediated the activation of neutrophils. The level of neutrophil activation correlated with antibody levels to MSP-1 and affinity-purified MSP-1 specific antibodies elicited ADRB activity. Furthermore, immunization of non-human primates with recombinant full-size MSP-1 induced antibodies, which efficiently opsonized merozoites. Reversing the function by pre-incubation with recombinant antigens allowed us to quantify the contribution of MSP-1 to the anti-parasitic effect of serum antibodies. Our data suggest that MSP-1 -- especially the partially conserved subunit MSP-1 - is a major target of opsonizing antibodies acquired during natural exposure to malaria. Induction of opsonizing antibodies might be a crucial effector mechanism for MSP-1-based malaria vaccines.