Multilaboratory approach to preclinical evaluation of vaccine immunogens for placental malaria

Pregnancy malaria is caused by Plasmodium falciparum-infected erythrocytes that adhere to the placental receptor chondroitin sulfate A (CSA) and sequester in the placenta; women become resistant to pregnancy malaria as they acquire antiadhesion antibodies that target surface proteins of placental parasites. VAR2CSA, a member of the P. falciparum EMP1 variant surface antigen family, is the leading candidate for a pregnancy malaria vaccine. Because VAR2CSA is a high-molecular-weight protein, a vaccine based on the full-length protein may not be feasible. An alternative approach has been to develop a vaccine targeting individual Duffy binding-like (DBL) domains. In this study, a consortium of laboratories under the Pregnancy Malaria Initiative compared the functional activity of antiadhesion antibodies elicited by different VAR2CSA domains and variants produced in prokaryotic and eukaryotic expression systems. Antisera were initially tested against laboratory lines of maternal parasites, and the most promising reagents were evaluated in the field against fresh placental parasite samples. Recombinant proteins expressed in Escherichia coli elicited antibody levels similar to those expressed in eukaryotic systems, as did the two allelic forms of the DBL4 and DBL5 domains. The procedures developed for this head-to-head comparison will be useful for future evaluation and down-selection of malaria vaccine immunogens. Fil: Fried, Michal. Seattle Biomedical Research Institute; Estados Unidos. Public Health Service. National Institute Of Health; Estados Unidos Fil: Avril, Marion. Seattle Biomedical Research Institute; Estados Unidos Fil: Chaturvedi, Richa. Seattle Biomedical Research Institute; Estados Unidos Fil: Fernandez, Pablo Mariano. Instituto Pasteur; Francia. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Lograsso, Joseph. Seattle Biomedical Research Institute; Estados Unidos Fil: Narum, David. Public Health Service. National Institute Of Health; Estados Unidos Fil: Nielsen, Morten A.. Universidad de Copenhagen; Dinamarca Fil: Oleinikov, Andrew V.. Seattle Biomedical Research Institute; Estados Unidos Fil: Resende, Mafalda. Universidad de Copenhagen; Dinamarca Fil: Salanti, Ali. Universidad de Copenhagen; Dinamarca Fil: Saveria, Tracy. Seattle Biomedical Research Institute; Estados Unidos Fil: Williamson, Kathryn. Seattle Biomedical Research Institute; Estados Unidos Fil: Dicko, Alassane. University of Bamako; Malí Fil: Scherf, Artur. Instituto Pasteur; Francia. Centre National de la Recherche Scientifique; Francia Fil: Smith, Joseph D.. Seattle Biomedical Research Institute; Estados Unidos Fil: Theander, Thor G. . Universidad de Copenhagen; Dinamarca Fil: Duffy, Patrick E.. Seattle Biomedical Research Institute; Estados Unidos. Public Health Service. National Institute Of Health; Estados Unidos