Autores
Andrew R Williams, Alexander D Douglas, Kazutoyo Miura, Joseph J Illingworth, Prateek Choudhary, Linda M Murungi, Julie M Furze, Ababacar Diouf, Olivo Miotto, Cecile Crosnier, Gavin J Wright, Dominic P Kwiatkowski, Rick M Fairhurst, Carole A Long, Simon J Draper
Fecha de publicación
2012/11/8
Revista
PLoS pathogens
Volumen
8
Número
11
Páginas
e1002991
Editor
Public Library of Science
Descripción
No vaccine has yet proven effective against the blood-stages of Plasmodium falciparum, which cause the symptoms and severe manifestations of malaria. We recently found that PfRH5, a P. falciparum-specific protein expressed in merozoites, is efficiently targeted by broadly-neutralizing, vaccine-induced antibodies. Here we show that antibodies against PfRH5 efficiently inhibit the in vitro growth of short-term-adapted parasite isolates from Cambodia, and that the EC50 values of antigen-specific antibodies against PfRH5 are lower than those against PfAMA1. Since antibody responses elicited by multiple antigens are speculated to improve the efficacy of blood-stage vaccines, we conducted detailed assessments of parasite growth inhibition by antibodies against PfRH5 in combination with antibodies against seven other merozoite antigens. We found that antibodies against PfRH5 act synergistically with antibodies against certain other merozoite antigens, most notably with antibodies against other erythrocyte-binding antigens such as PfRH4, to inhibit the growth of a homologous P. falciparum clone. A combination of antibodies against PfRH4 and basigin, the erythrocyte receptor for PfRH5, also potently inhibited parasite growth. This methodology provides the first quantitative evidence that polyclonal vaccine-induced antibodies can act synergistically against P. falciparum antigens and should help to guide the rational development of future multi-antigen vaccines.
Citas totales
201220132014201520162017201820192020202111015211716111166