Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

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...

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Bibliographic Details
Published in:PloS one 2019-09, Vol.14 (9), p.e0221733-e0221733
Main Authors: Chan, Jo-Anne, Wetzel, David, Reiling, Linda, Miura, Kazutoyo, Drew, Damien R, Gilson, Paul R, Anderson, David A, Richards, Jack S, Long, Carole A, Suckow, Manfred, Jenzelewski, Volker, Tsuboi, Takafumi, Boyle, Michelle J, Piontek, Michael, Beeson, James G
Format: Article
Language:English
Subjects:
Analysis
Animals
Anopheles - parasitology
Antibodies
Antibody Affinity
Antigen presentation
Antigens
Aquatic birds
Biology and Life Sciences
Biotechnology
Clinical trials
Cyclic GMP
Disease transmission
Drug resistance
Effectiveness
Erythrocytes
Gametocytes
Global health
HEK293 Cells
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatitis B virus - genetics
Humans
Immunity
Immunogenicity
Immunoglobulins
Immunology
Infectious diseases
Laboratories
Life sciences
Malaria
Malaria vaccines
Malaria Vaccines - genetics
Malaria Vaccines - immunology
Medicine and Health Sciences
Mosquito Vectors - parasitology
Mosquitoes
Parasites
Pichia - genetics
Pichia - metabolism
Plasmodium falciparum
Plasmodium falciparum - genetics
Plasmodium falciparum - immunology
Plasmodium falciparum - pathogenicity
Prevention
Proteins
Protozoan Proteins - genetics
Protozoan Proteins - immunology
Rabbits
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Research and Analysis Methods
Risk factors
Treatment outcome
Vaccine development
Vaccine efficacy
Vaccines
Vaccines, Virus-Like Particle - genetics
Vaccines, Virus-Like Particle - immunology
Vector-borne diseases
Viral Proteins - genetics
Viral Proteins - metabolism
Virus-like particles
Viruses
World health
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0221733