Autor/a:
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Franca, Camila T.; Hostetler, Jessica B.; Sharma, Sumana; White, Michael T.; Lin, Enmoore; Kiniboro, Benson; Waltmann, Andreea; Darcy, Andrew W.; Li Wai Suen, Connie S. N.; Siba, Peter; King, Christopher L.; Rayner, Julian C.; Fairhurst, Rick M.; Mueller, Ivo
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Abstract:
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BACKGROUND: Elimination of Plasmodium vivax malaria would be
greatly facilitated by the development of an effective vaccine.
A comprehensive and systematic characterization of antibodies to
P. vivax antigens in exposed populations is useful in guiding
rational vaccine design. METHODOLOGY/PRINCIPAL FINDINGS: In this
study, we investigated antibodies to a large library of P. vivax
entire ectodomain merozoite proteins in 2 Asia-Pacific
populations, analysing the relationship of antibody levels with
markers of current and cumulative malaria exposure, and
socioeconomic and clinical indicators. 29 antigenic targets of
natural immunity were identified. Of these, 12
highly-immunogenic proteins were strongly associated with age
and thus cumulative lifetime exposure in Solomon Islanders
(P<0.001-0.027). A subset of 6 proteins, selected on the
basis of immunogenicity and expression levels, were used to
examine antibody levels in plasma samples from a population of
young Papua New Guinean children with well-characterized
individual differences in exposure. This analysis identified a
strong association between reduced risk of clinical disease and
antibody levels to P12, P41, and a novel hypothetical protein
that has not previously been studied, PVX_081550 (IRR 0.46-0.74;
P<0.001-0.041). CONCLUSION/SIGNIFICANCE: These data emphasize
the benefits of an unbiased screening approach in identifying
novel vaccine candidate antigens. Functional studies are now
required to establish whether PVX_081550 is a key component of
the naturally-acquired protective immune response, a biomarker
of immune status, or both. |