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

Autor: Douglas AD; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. sandy.douglas@ndm.ox.ac.uk., Baldeviano GC; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Jin J; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Miura K; Laboratory of Malaria and Vector Research, NIAID/NIH, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA., Diouf A; Laboratory of Malaria and Vector Research, NIAID/NIH, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA., Zenonos ZA; Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK., Ventocilla JA; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Silk SE; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Marshall JM; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Alanine DGW; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Wang C; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Edwards NJ; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK., Leiva KP; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Gomez-Puerta LA; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Lucas CM; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Wright GJ; Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Cambridge, CB10 1SA, UK., Long CA; Laboratory of Malaria and Vector Research, NIAID/NIH, 12735 Twinbrook Parkway, Rockville, MD, 20852, USA., Royal JM; US Naval Medical Research Unit No. 6 (NAMRU-6), Av. Venezuela Cuadra 36, Bellavista, Callao, Peru., Draper SJ; Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, OX3 7DQ, UK. simon.draper@ndm.ox.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2019 Apr 26; Vol. 10 (1), pp. 1953. Date of Electronic Publication: 2019 Apr 26.
DOI: 10.1038/s41467-019-09894-4
Abstrakt: 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.
Databáze: MEDLINE
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