ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1675780
This article is part of the Research TopicInnovative Vaccine Development Strategies for Parasitic DiseasesView all 4 articles
Subcutaneous Administration of the Malaria R21/Matrix M vaccine and Immune Complex Formation with anti-CircumSporozoite Protein mAb 2A10 elicit Protective Efficacy in Mice
Provisionally accepted
- University of Oxford, Oxford, United Kingdom
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R21, the most efficacious malaria vaccine to date, has been recommended by the World Health Organization (WHO) for the prevention of malaria in children. The current vaccination schedule requires three intramuscular doses per year. Optimizing vaccine administration strategies, including exploring alternative routes of immunization and novel vaccine formulations, has the potential to reduce the number of required doses to achieve high efficacy. Immune complexes (ICs), formed by combining antigens with their cognate antibodies, have been successfully employed in licensed poultry vaccines for viral diseases and are showing promise in preclinical studies for human viral vaccines. Co-delivery of antigen with immune complexes has been reported to enhance antibody titers in preclinical models. Here, we present the first report of the immunogenicity and short-term high protective efficacy (100% in BALB/c mice) of R21/Matrix-M administered via the subcutaneous (SC) route, as well as in a modified formulation as an immune complex (R21: anti-NANP mAb 2A10) with only two immunizations. We also evaluated co-administration of R21 with pre-formed ICs. While IC-based vaccination strategies have primarily been explored for viral diseases, this study represents the first application of this approach to a parasitic disease. Our findings provide new insights into the potential of alternative vaccine delivery strategies and immune complex platforms for improving malaria vaccination outcomes.
Keywords: Vaccine, Malaria, Immune-complex, antibody, protection
Received: 29 Jul 2025; Accepted: 10 Sep 2025.
Copyright: © 2025 Mukhopadhyay, Camacho, Hill and Salman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ekta Mukhopadhyay, University of Oxford, Oxford, United Kingdom
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