Background Malaria transmission blocking vaccines (TBV) hold the potential to block malaria transmission in the population thereby contributing to malaria elimination by producing specific antibodies against functionally important proteins expressed during parasite development in the mosquito. The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are leading candidates for a malaria TBV, while the Circumsporozoite Protein (CSP) remains the leading candidate for an anti-infection Vaccine.

Methods A scalable and reproducible product process in Lactococcus lactis was developed for two candidates: R0.6C (a first-generation TBV) and ProC6C (a novel fusion protein, developed as a multi-stage malaria vaccine). Preclinical development led to a dual-adjuvant design for clinical evaluation, where the antigen is absorbed to Alhydrogel® and either administered directly or mixed at the bedside with the Matrix-M™ Adjuvant. A first-in-human Phase 1 study, conducted in Burkina Faso adults, evaluated R0.6C and ProC6C (at two dose levels, 30/100 µg) formulated on Alhydrogel® alone or in combination with Matrix-M (15/50 µg).

Results This clinical study demonstrated that both antigens, regardless of dosage, on either formulation were safe and well tolerated. Serology conducted against the immunogen, demonstrated that the addition of Matrix-M enhanced the immune response in adult Burkinabes, compared to Alhydrogel® alone. The functional antibody response, evaluated by an independent laboratory, demonstrated that R0.6C induces sporadic transmission reducing antibodies (TRA). In comparison, ProC6C induced significant transmission reducing antibodies (>75% TRA in > 75% of the cohort).

Conclusion These results demonstrate that malaria proteins, produced L. lactis and when formulated on Alhydrogel® alone or in combination with Matrix-M are safe, well tolerated and immunogenic. The immunogenicity of ProC6C and its functional antibody response, lays the foundation for further clinical development of this novel chimeric antigen. This project is part of the EDCTP2 Programme supported by the European Union and Developing Countries Clinical Trials Partnership (Grant number RIA2018SV-2311).