Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA
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Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA. / 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.
In: Lab Animal, Vol. 52, No. 12, 2023, p. 315-323.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA
AU - Doritchamou, Justin
AU - Nielsen, Morten A.
AU - Chêne, Arnaud
AU - Viebig, Nicola K.
AU - Lambert, Lynn E.
AU - Sander, Adam F.
AU - Semblat, Jean Philippe
AU - Hundt, Sophia
AU - Orr-Gonzalez, Sachy
AU - Janitzek, Christoph Mikkel
AU - Spiegel, Alicia J.
AU - Clemmensen, Stine B.
AU - Thomas, Marvin L.
AU - Nason, Martha C.
AU - Snow-Smith, Maryonne
AU - Barnafo, Emma K.
AU - Shiloach, Joseph
AU - Chen, Beth B.
AU - Nadakal, Steven
AU - Highsmith, Kendrick
AU - Ouahes, Tarik
AU - Conteh, Solomon
AU - Sharma, Ankur
AU - Torano, Holly
AU - Butler, Brandi
AU - Reiter, Karine
AU - Rausch, Kelly M.
AU - Scaria, Puthupparampil V.
AU - Anderson, Charles
AU - Narum, David L.
AU - Salanti, Ali
AU - Fried, Michal
AU - Theander, Thor G.
AU - Gamain, Benoit
AU - Duffy, Patrick E.
N1 - Publisher Copyright: © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41684-023-01274-2
DO - 10.1038/s41684-023-01274-2
M3 - Journal article
C2 - 37932470
AN - SCOPUS:85175798368
VL - 52
SP - 315
EP - 323
JO - Lab Animal
JF - Lab Animal
SN - 0093-7355
IS - 12
ER -
ID: 373884387