Malaria immunisation beyond subunit vaccines: Current progress

Subunit vaccines against malaria target the circumsporozoite protein, and two vaccines are currently licensed: RTS,S/AS01 and R21/Matrix-M. However, their limitation is that they only provide protection against Plasmodium falciparum. Prof. Miguel Prudêncio (University of Lisbon, Portugal) reviewed additional vaccine strategies aimed at extending protection beyond P. falciparum [1]. 

An alternative to subunit vaccines is whole-sporozoite vaccination. “As the name indicates, these vaccines rely on the sporozoite itself. This has been achieved for P. falciparum by attenuating this parasite, but the same approach is not feasible for P. vivax”, said Prof. Prudêncio. One such candidate for P. falciparum vaccination is PbVac, which uses genetically modified P. berghei, a rodent malaria parasite that is not pathogenic to humans. In a phase 1/2 trial, PbVac demonstrated acceptable safety and tolerability, achieving a 95% reduction in P. falciparum parasite density in the liver, along with dose-dependent cross-species cellular immune responses and functional antibody production [2].  

Based on this concept, the PbviVac platform was developed, using P. berghei parasites that have been genetically modified to express selected P. vivax proteins in addition to the P. vivax circumsporozoite protein. In preclinical studies, PbviVacTRAP, which incorporates the thrombospondin adhesion protein (TRAP) involved in salivary gland invasion, sporozoite motility, and host-cell interaction, demonstrated immunogenicity and protective efficacy in non-human primates. It induced antibodies against both the circumsporozoite and TRAP proteins, along with robust cellular responses against TRAP. Another candidate vaccine, PbviVacPvs25, expresses the Pvs25 protein,  essential for parasite survival and epithelial penetration in the mosquito. In mouse models, PbviVacPvs25 triggered antibodies targeting both the circumsporozoite and Pvs25 proteins [1].  

“In summary, PbVac established proof-of-concept for whole-sporozoite vaccination against malaria using P. falciparum as the target and clinically validated this approach,” said Prof. Prudêncio. “For P. vivax, we now have three constructs at different stages of development.” 

1. Prudêncio M. Recent advances in malaria vaccination: Innovations & impact. 6th ESCMID Vaccines, 10–13 September 2025, Lisbon, Portugal. 


2. Reuling IJ, et al. Sci Transl Med. 2020;12(544):eaay2578. 

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Posted on 21 October 2025