AUTHOR=de Graaf Hans , Payne Ruth O. , Taylor Iona , Miura Kazutoyo , Long Carol A. , Elias Sean C. , Zaric Marija , Minassian Angela M. , Silk Sarah E. , Li Lee , Poulton Ian D. , Baker Megan , Draper Simon J. , Gbesemete Diane , Brendish Nathan J. , Martins Filipa , Marini Arianna , Mekhaiel David , Edwards Nick J. , Roberts Rachel , Vekemans Johan , Moyle Sarah , Faust Saul N. , Berrie Eleanor , Lawrie Alison M. , Hill Fergal , Hill Adrian V. S. , Biswas Sumi TITLE=Safety and Immunogenicity of ChAd63/MVA Pfs25-IMX313 in a Phase I First-in-Human Trial JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.694759 DOI=10.3389/fimmu.2021.694759 ISSN=1664-3224 ABSTRACT=Background

Transmission blocking vaccines targeting the sexual-stages of the malaria parasite could play a major role to achieve elimination and eradication of malaria. The Plasmodium falciparum Pfs25 protein (Pfs25) is the most clinically advanced candidate sexual-stage antigen. IMX313, a complement inhibitor C4b-binding protein that forms heptamers with the antigen fused to it, improve antibody responses. This is the first time that viral vectors have been used to induce antibodies in humans against an antigen that is expressed only in the mosquito vector.

Methods

Clinical trial looking at safety and immunogenicity of two recombinant viral vectored vaccines encoding Pfs25-IMX313 in healthy malaria-naive adults. Replication-deficient chimpanzee adenovirus serotype 63 (ChAd63) and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding Pfs25-IMX313, were delivered by the intramuscular route in a heterologous prime-boost regimen using an 8-week interval. Safety data and samples for immunogenicity assays were taken at various time-points.

Results

The reactogenicity of the vaccines was similar to that seen in previous trials using the same viral vectors encoding other antigens. The vaccines were immunogenic and induced both antibody and T cell responses against Pfs25, but significant transmission reducing activity (TRA) was not observed in most volunteers by standard membrane feeding assay.

Conclusion

Both vaccines were well tolerated and demonstrated a favorable safety profile in malaria-naive adults. However, the transmission reducing activity of the antibodies generated were weak, suggesting the need for an alternative vaccine formulation.

Trial Registration

Clinicaltrials.gov NCT02532049.