Combatting seasonal malaria transmission using a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody

Transmission-blocking interventions can play an important role in combatting malaria worldwide. Recently, a highly potent Plasmodium falciparum transmission-blocking monoclonal antibody (TB31F) was demonstrated to be safe and efficacious in malaria-naïve volunteers. Here we determine what dose would be required to obtain effective transmission reduction throughout the malaria season and predict the potential public health impact of large-scale implementation of TB31F alongside existing interventions. To this purpose, we developed a pharmaco-epidemiological model, tailored to two settings of differing transmission intensity with already established insecticide-treated nets and seasonal malaria chemoprevention interventions. We found that a simple weight-based TB31F dosing strategy achieved >80% transmission-reducing activity for over 5 months. With this approach, community-wide annual administration (at 80% coverage) of TB31F over a three-year period was predicted to reduce clinical incidence by 54% (381 cases averted per 1000 people per year) in a high-transmission seasonal setting, and 74% (157 cases averted per 1000 people per year) in a low-transmission seasonal setting. Targeting school-aged children gave the largest reduction in terms of cases averted per dose. We conclude that annual administration of transmission-blocking mAb TB31F may be an effective intervention against malaria in seasonal malaria settings. What is already known on this topic What this study adds How this study might affect research, practice or policy ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was supported by a fellowship from the European Research Council to T.B. (ERC-CoG 864180) and PATH Malaria Vaccine Initiative, Washington DC, US. JDC, GDC and TSC acknowledge funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 programme supported by the European Union. GDC acknowledges funding from the Wellcome Trust (reference 220900/Z/20/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study received approval from the Arnhem-Nijmegen Committee on Research Involving Human Subjects (NL69779.091.19). The trial is registered with ClinicalTrials.gov under identifier [NCT04238689][1]. The study was conducted in accordance with the latest Fortaleza revision of the Declaration of Helsinki (2013), the Netherlands Medical Research Involving Human Subjects Act, ICH Good Clinical Practice standards, and local regulatory requirements. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The modelling code used to generate the results presented here will be made available upon publication [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04238689&atom=%2Fmedrxiv%2Fearly%2F2022%2F09%2F14%2F2022.09.11.22279612.atom