Pfs230 Domain 7 is targeted by a potent malaria transmission-blocking monoclonal antibody

Maartje R Inklaar; Roos M de Jong; Ezra T Bekkering; Hikaru Nagaoka; Felix L Fennemann; Karina Teelen; Marga van de Vegte-Bolmer; Geert-Jan van Gemert; Rianne Stoter; C Richter King; Nicholas I Proellochs; Teun Bousema; Eizo Takashima; Takafumi Tsuboi; Matthijs M Jore

doi:10.1038/s41541-023-00784-x

Pfs230 Domain 7 is targeted by a potent malaria transmission-blocking monoclonal antibody

NPJ Vaccines. 2023 Dec 12;8(1):186. doi: 10.1038/s41541-023-00784-x.

Authors

Affiliations

¹ Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands.
² Division of Malaria Research, Proteo-Science Center, Ehime University, Matsuyama, Japan.
³ Department of Tumor Immunology, Radboud University Medical Center, Nijmegen, The Netherlands.
⁴ Center for Vaccine Innovation and Access, PATH, Washington, DC, USA.
⁵ Division of Cell-Free Sciences, Proteo-Science Center, Ehime University, Matsuyama, Japan.
⁶ Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands. Matthijs.Jore@radboudumc.nl.

^# Contributed equally.

Abstract

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that block Plasmodium parasite development in the mosquito midgut, thus preventing mosquitoes from becoming infectious. While the Pro-domain and first of fourteen 6-Cysteine domains (Pro-D1) of the Plasmodium gamete surface protein Pfs230 are known targets of transmission-blocking antibodies, no studies to date have discovered other Pfs230 domains that are functional targets. Here, we show that a murine monoclonal antibody (mAb), 18F25.1, targets Pfs230 Domain 7. We generated a subclass-switched complement-fixing variant, mAb 18F25.2a, using a CRISPR/Cas9-based hybridoma engineering method. This subclass-switched mAb 18F25.2a induced lysis of female gametes in vitro. Importantly, mAb 18F25.2a potently reduced P. falciparum infection of Anopheles stephensi mosquitoes in a complement-dependent manner, as assessed by standard membrane feeding assays. Together, our data identify Pfs230 Domain 7 as target for transmission-blocking antibodies and provide a strong incentive to study domains outside Pfs230Pro-D1 as TBV candidates.