Journal
SCIENTIFIC REPORTS
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/srep18848
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Funding
- UK Medical Research Council [G1000527]
- UK MRC
- UK Department for International Development (DFID)
- National Institute of Allergy and Infectious Diseases/NIH
- PATH Malaria Vaccine Initiative
- Wellcome Trust [106917/Z/15/Z] Funding Source: Wellcome Trust
- Medical Research Council [G1000527] Funding Source: researchfish
- Wellcome Trust [106917/Z/15/Z] Funding Source: researchfish
- MRC [G1000527] Funding Source: UKRI
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Transmission-blocking vaccines (TBV) target the sexual-stages of the malaria parasite in the mosquito midgut and are widely considered to be an essential tool for malaria elimination. High-titer functional antibodies are required against target antigens to achieve effective transmission-blocking activity. We have fused Pfs25, the leading malaria TBV candidate antigen to IMX313, a molecular adjuvant and expressed it both in ChAd63 and MVA viral vectors and as a secreted protein-nanoparticle. Pfs25-IMX313 expressed from viral vectors or as a protein-nanoparticle is significantly more immunogenic and gives significantly better transmission-reducing activity than monomeric Pfs25. In addition, we demonstrate that the Pfs25-IMX313 protein-nanoparticle leads to a qualitatively improved antibody response in comparison to soluble Pfs25, as well as to significantly higher germinal centre (GC) responses. These results demonstrate that antigen multimerization using IMX313 is a very promising strategy to enhance antibody responses against Pfs25, and that Pfs25-IMX313 is a highly promising TBV candidate vaccine.
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