Evaluating the potential of cross-species neutralization of anti-PfCyRPA and anti-PfRIPR Monoclonal Antibodies

Guerra, N.; Hagadorn, K. A.; Nair, M.; Thiam, L. G.; Williams, B. G.; McHugh, K.; Pipini, D.; Healer, J.; Masendycz, P.; Cowman, A. F.; Draper, S. J.; Bei, A. K.

doi:10.1101/2025.11.03.682341

bioRxiv · 10.1101/2025.11.03.682341

Evaluating the potential of cross-species neutralization of anti-PfCyRPA and anti-PfRIPR Monoclonal Antibodies

Guerra, N.·Hagadorn, K. A.·Nair, M.·Thiam, L. G.·Williams, B. G.·McHugh, K.·Pipini, D.·Healer, J.·Masendycz, P.·Cowman, A. F.·Draper, S. J.·Bei, A. K.

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Abstract

PfCyRPA and PfRIPR are promising next-generation malaria blood-stage vaccine candidate antigens that play an essential role in erythrocyte invasion of Plasmodium falciparum. CyRPA and RIPR orthologs are present in all human-infecting Plasmodium species, suggesting the potential for a cross-species vaccine. Using Growth Inhibition Assays (GIA), this study investigates seven anti-PfCyRPA and three anti-PfRIPR monoclonal antibodies targeting P. falciparum for their inhibitory activity against P. knowlesi, a non-falciparum species that contributes to a significant burden of zoonotic disease in South-East Asia, shares some biological features with Plasmodium vivax, and has a robust in vitro culture system. Despite their efficacy against P. falciparum and partially conserved epitopes, these antibodies exhibited minimal inhibition of P. knowlesi. Understanding the antigenic diversity and immune mechanisms across Plasmodium species is critical for advancing pan-species vaccine strategies.

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Guerra, N., Hagadorn, K. A., Nair, M., Thiam, L. G., Williams, B. G., McHugh, K., Pipini, D., Healer, J., Masendycz, P., Cowman, A. F., Draper, S. J., Bei, A. K.. 2025-11-04. Evaluating the potential of cross-species neutralization of anti-PfCyRPA and anti-PfRIPR Monoclonal Antibodies. https://doi.org/10.1101/2025.11.03.682341

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