Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA.
СтатьяResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Doritchamou Justin, Nielsen Morten A, Chêne Arnaud, Viebig Nicola K, Lambert Lynn E, Sander Adam F, Semblat Jean-Philippe, Hundt Sophia, Orr-Gonzalez Sachy, Janitzek Christoph Mikkel, Spiegel Alicia J, Clemmensen Stine B, Thomas Marvin L, Nason Martha C, Snow-Smith Maryonne, Barnafo Emma K, Shiloach Joseph, Chen Beth B, Nadakal Steven, Highsmith Kendrick, Ouahes Tarik, Conteh Solomon, Sharma Ankur, Torano Holly, Butler Brandi, Reiter Karine, Rausch Kelly M, Scaria Puthupparampil V, Anderson Charles, Narum David L, Salanti Ali, Fried Michal, Theander Thor G, Gamain Benoit, Duffy Patrick E
Аннотация
Placental malaria vaccines (PMVs) are being developed to prevent severe sequelae of placental malaria (PM) in pregnant women and their offspring. The leading candidate vaccine antigen VAR2CSA mediates parasite binding to placental receptor chondroitin sulfate A (CSA). Despite promising results in small animal studies, recent human trials of the first two PMV candidates (PAMVAC and PRIMVAC) generated limited cross-reactivity and cross-inhibitory activity to heterologous parasites. Here we immunized Aotus nancymaae monkeys with three PMV candidates (PAMVAC, PRIMVAC and ID1-ID2a_M1010) adjuvanted with Alhydrogel, and exploited the model to investigate boosting of functional vaccine responses during PM episodes as well as with nanoparticle antigens. PMV candidates induced high levels of antigen-specific IgG with significant cross-reactivity across PMV antigens by enzyme-linked immunosorbent assay. Conversely, PMV antibodies recognized native VAR2CSA and blocked CSA adhesion of only homologous parasites and not of heterologous parasites. PM episodes did not significantly boost VAR2CSA antibody levels or serum functional activity; nanoparticle and monomer antigens alike boosted serum reactivity but not functional activities. Overall, PMV candidates induced functional antibodies with limited heterologous activity in Aotus monkeys, similar to responses reported in humans. The Aotus model appears suitable for preclinical downselection of PMV candidates and assessment of antibody boosting by PM episodes.