Aotus nancymaae model predicts human immune response to the placental malaria vaccine candidate VAR2CSA

被引：1

作者：

Doritchamou, Justin ^{[1
]}

Nielsen, Morten A. ^{[2
,3
]}

Chene, Arnaud ^{[4
,5
]}

Viebig, Nicola K. ^{[6
]}

Lambert, Lynn E. ^{[1
]}

Sander, Adam F. ^{[2
,3
]}

Semblat, Jean-Philippe ^{[4
,5
]}

Hundt, Sophia ^{[6
]}

Orr-Gonzalez, Sachy ^{[1
]}

Janitzek, Christoph Mikkel ^{[2
,3
]}

Spiegel, Alicia J. ^{[1
]}

Clemmensen, Stine B. ^{[7
]}

Thomas, Marvin L. ^{[8
]}

Nason, Martha C. ^{[9
]}

Snow-Smith, Maryonne ^{[1
]}

Barnafo, Emma K. ^{[1
]}

Shiloach, Joseph ^{[10
]}

Chen, Beth B. ^{[1
,4
]}

Nadakal, Steven ^{[1
]}

Highsmith, Kendrick ^{[1
]}

Ouahes, Tarik ^{[1
]}

Conteh, Solomon ^{[1
]}

Sharma, Ankur ^{[1
]}

Torano, Holly ^{[1
]}

Butler, Brandi ^{[1
]}

Reiter, Karine ^{[1
]}

Rausch, Kelly M. ^{[1
]}

Scaria, Puthupparampil V. ^{[1
]}

Anderson, Charles ^{[1
]}

Narum, David L. ^{[1
]}

Salanti, Ali ^{[2
,3
]}

Fried, Michal ^{[1
]}

Theander, Thor G. ^{[2
,3
]}

Gamain, Benoit ^{[5
]}

Duffy, Patrick E. ^{[1
]}

机构：

[1] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20894 USA

[2] Univ Copenhagen, Dept Immunol & Microbiol, Ctr Med Parasitol, Copenhagen, Denmark

[3] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen, Denmark

[4] Univ Paris Cite, Paris, France

[5] Univ Antilles, INSERM, BIGR, Paris, France

[6] Univ Klinikum Heidelberg, European Vaccine Initiat, Heidelberg, Germany

[7] ExpreS2ion Biotechnol, Horsholm, Denmark

[8] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD USA

[9] NIAID, Biostat Res Branch, Div Clin Res, NIH, Bethesda, MD USA

[10] Natl Inst Diabet & Digest & Kidney Dis, Biotechnol Unit, Bethesda, MD USA

来源：

LAB ANIMAL | 2023年 / 52卷 / 12期

基金：

美国国家卫生研究院;

关键词：

PLASMODIUM-FALCIPARUM ADHESION; CHONDROITIN SULFATE-A; NTS-DBL2X REGION; PREGNANT-WOMEN; ANTIBODIES; PROTECTION; SURFACE; INFECTION; ADHERENCE; ANTIGENS;

D O I：

10.1038/s41684-023-01274-2

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

0906 ;

摘要：

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.

引用

页码：315 / +

页数：17

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