Malaria, caused by Plasmodium falciparum, remains one of the most devastating parasitic diseases globally, particularly affecting vulnerable populations in tropical and subtropical regions. While repeated natural infections gradually confer partial immunity, the long-standing goal of immunological interventions has been to achieve robust, infection-preventing immunity. Despite the licensing of two subunit vaccines—RTS,S/AS01 (Mosquirix) and R21/Matrix-M—that target the conserved P. falciparumcircumsporozoite protein (PfCSP), their moderate efficacy against clinical malaria underscores the need for next-generation immunoprophylactic solutions.
Recognizing this need, researchers at the BRIC-National Institute of Immunology (NII), New Delhi, have focused on the development of monoclonal antibodies (mAbs) as a novel and potent alternative to traditional vaccines. Monoclonal antibodies are highly specific, laboratory-engineered proteins that bind to defined epitopes and can offer immediate protection upon administration. These biologics are emerging as key players in the prevention of infectious diseases, including malaria, particularly in scenarios where rapid-onset or short-term immunity is essential.
Using a phage display-based fully human antibody library, the NII team in collaboration with ICGEB successfully targeted recombinant PfCSP (rPfCSP) and isolated two novel monoclonal antibodies, CL1 and CL3, with potent antimalarial activity. These antibodies demonstrated >80% inhibition of sporozoite infectivity in vivo following a single 50 µg dose per host in rodent challenge models. This high level of protection, achieved with a single administration, highlights the feasibility of using these mAbs as part of malaria immunoprophylaxis programs.
The therapeutic potential of CL1 and CL3 extends across multiple high-risk contexts—travellers, military personnel, pregnant women, infants during peak transmission seasons, and patients recovering from severe malaria. Given their immediate onset of action and simplicity of delivery, these antibodies could also support malaria elimination efforts in endemic regions through targeted interventions.
This work represents a critical milestone in India’s indigenous malaria research pipeline and complements ongoing global efforts toward malaria control and eradication.
NII and its collaborators have actively contributed to India’s innovation landscape in malaria vaccine development, securing patents that reflect cutting-edge translational research. These innovations collectively underscore India’s growing leadership in the global malaria vaccine R&D ecosystem.
References:
1. Patent No. 508461 (Granted, 08/02/2024): “A Chaperon Family Protein Based Malaria Vaccine” by Agam Prasad Singh et al., owned by BRIC-NII.
2. Parveen S, Rath PP, Tabrez S, Khan S, Singh P, Arkam SZ, Verma S, Ahmad S, Singh SK, Junaid IT, Kumar D, Theisen M, Gupta D, Mohmmed A, Salunke DM, Singh AP, Malhotra P. Novel, fully human, anti-PfCSP antibodies with potent antimalarial activity using a phage display-based strategy. Vaccine. 54:126993.
With inputs from Dr Agam Prasad Singh