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- Title
A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates.
- Authors
Douglas, Alexander D.; Baldeviano, G. Christian; Jin, Jing; Miura, Kazutoyo; Diouf, Ababacar; Zenonos, Zenon A.; Ventocilla, Julio A.; Silk, Sarah E.; Marshall, Jennifer M.; Alanine, Daniel G. W.; Wang, Chuan; Edwards, Nick J.; Leiva, Karina P.; Gomez-Puerta, Luis A.; Lucas, Carmen M.; Wright, Gavin J.; Long, Carole A.; Royal, Joseph M.; Draper, Simon J.
- Abstract
Malaria vaccine design and prioritization has been hindered by the lack of a mechanistic correlate of protection. We previously demonstrated a strong association between protection and merozoite-neutralizing antibody responses following vaccination of non-human primates against Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). Here, we test the mechanism of protection. Using mutant human IgG1 Fc regions engineered not to engage complement or FcR-dependent effector mechanisms, we produce merozoite-neutralizing and non-neutralizing anti-PfRH5 chimeric monoclonal antibodies (mAbs) and perform a passive transfer-P. falciparum challenge study in Aotus nancymaae monkeys. At the highest dose tested, 6/6 animals given the neutralizing PfRH5-binding mAb c2AC7 survive the challenge without treatment, compared to 0/6 animals given non-neutralizing PfRH5-binding mAb c4BA7 and 0/6 animals given an isotype control mAb. Our results address the controversy regarding whether merozoite-neutralizing antibody can cause protection against P. falciparum blood-stage infections, and highlight the quantitative challenge of achieving such protection. Proof of protection against blood-stage P. falciparum malaria by a single immunological mechanism has been elusive. Here, using engineered anti-PfRH5 chimeric monoclonal antibodies in non-human primates, the authors show that high levels of merozoite-neutralizing antibodies can achieve protection.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, pN.PAG
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-019-09894-4