A defined mechanistic correlate of protection against Plasmodium falciparum malaria in non-human primates.

Alexander D Douglas, G Christian Baldeviano, Jing Jin, Kazutoyo Miura, Ababacar Diouf, Zenon A Zenonos, Julio A Ventocilla, Sarah E Silk, Jennifer M Marshall, Daniel G W Alanine, Chuan Wang, Nick J Edwards, Karina P Leiva, Luis A Gomez-Puerta, Carmen M Lucas, Gavin J Wright, Carole A Long, Joseph M Royal, Simon J Draper

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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.
Original languageEnglish
Article number1953
Number of pages8
JournalNature Communications
Issue number1
Publication statusPublished - 26 Apr 2019


  • parasites and microbes
  • staffpaper

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