Identification of a Protective Non-CSP Epitope for Enhanced Malaria Vaccine Strategies 4780

Abstract Description Malaria, caused by Plasmodium parasites and transmitted by Anopheles mosquitoes, remains a major global health issue, with 249 million cases and 608,000 deaths reported in 2022. Malaria vaccine development is hindered by the parasite’s complex life cycle and antigenic variation, making sporozoite targeting during the pre-erythrocytic stage an ideal strategy for preventing infection and transmission. The circumsporozoite protein (CSP), the main sporozoite surface protein, is the focus of current pre-erythrocytic vaccines. The CSP-based RTS,S/AS01 vaccine, approved by WHO in 2021, marked a significant milestone, yet its efficacy leaves room for improvement. Whole sporozoite vaccine (WSV) strategies provide broader protection, emphasizing the need to explore non-CSP antigens. However, protective epitopes beyond CSP are poorly understood. To address this, we used a WSV strategy, immunizing mice with live Plasmodium falciparum sporozoites and identifying non-CSP-specific monoclonal antibodies (mAbs) via hybridoma technology. Screening 10,000 B-cell candidates yielded ∼5% non-CSP binders, including 14G3, which cross-reacted with P. falciparum and P. berghei. Western blot analysis showed 14G3 binding a multimeric structure under non-reducing conditions, indicating a structural epitope. Notably, 14G3 reduced sporozoite invasion and delayed parasitemia in a mouse model. This protective non-CSP epitope is a promising candidate for combination vaccine strategies against malaria. Topic Categories Vaccines and Immunotherapy (VAC)