Abstract
The development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anopheles / parasitology
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Antibody Affinity
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HEK293 Cells
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Hepatitis B virus / genetics
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Humans
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Malaria Vaccines / genetics
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Malaria Vaccines / immunology*
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Mosquito Vectors / parasitology
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Pichia / genetics
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Pichia / metabolism
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Plasmodium falciparum / genetics
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Plasmodium falciparum / immunology
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Plasmodium falciparum / pathogenicity
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Rabbits
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Recombinant Proteins / genetics
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Recombinant Proteins / immunology*
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Vaccines, Virus-Like Particle / genetics
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Vaccines, Virus-Like Particle / immunology*
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Viral Proteins / genetics
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Viral Proteins / metabolism
Substances
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Malaria Vaccines
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Protozoan Proteins
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Recombinant Proteins
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Vaccines, Virus-Like Particle
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Viral Proteins
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transmission-Blocking Vaccine based on Pfs25
Grants and funding
Funding was provided by PATH Malaria Vaccine Initiative and the National Health and Medical Research Council (NHMRC) of Australia (Senior Research Fellowship and Program Grant to JB, Career Development Fellowship to MB). Burnet Institute is supported by funding from the NHMRC Independent Research Institutes Infrastructure Support Scheme and a Victorian State Government Operational Infrastructure grant. The SMFA work performed here was supported was supported in part by the intramural program of the National Institute of Allergy and Infectious Diseases/NIH. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. ARTES Biotechnology GmbH provided support in the form of salaries for authors (DW, MS, VJ and MP) and generation of VLPs, but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The specific roles of these authors are articulated in the ‘Author Contributions’ section.