Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax

Autor: Iona J. Brian, Jessica A. Chichester, Hong Bi, Sara E. Zakutansky, R.M. Jones, Andrew M. Blagborough, Vidadi Yusibov, Leanna M. Upton, Konstantin Musiychuk, J. Sattabonkot, Katarzyna A. Sala, Stephen J. Streatfield, Robert E. Sinden, Sumi Biswas
Přispěvatelé: Medical Research Council (MRC), Publica
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Plasmodium
Immunogen
medicine.medical_treatment
Plasmodium vivax
Protozoan Proteins
Nicotiana benthamiana
0302 clinical medicine
Plant-produced antigen
Mice
Inbred BALB C
Vaccines
Synthetic
biology
Immunogenicity
11 Medical And Health Sciences
Pvs25
Plants
Genetically Modified
Recombinant Proteins
3. Good health
Vaccination
Infectious Diseases
Vaccines
Subunit
Molecular Medicine
Female
Adjuvant
Transmission blocking vaccine
030231 tropical medicine
Immunization
Secondary
Heterologous
Subunit vaccine
Article
Viral vector
03 medical and health sciences
Adjuvants
Immunologic
Virology
Immunology and Microbiology(all)
parasitic diseases
Malaria Vaccines
Tobacco
medicine
Malaria
Vivax
Animals
General Veterinary
General Immunology and Microbiology
Public Health
Environmental and Occupational Health
06 Biological Sciences
biology.organism_classification
veterinary(all)
Malaria
030104 developmental biology
Chromobox Protein Homolog 5
07 Agricultural And Veterinary Sciences
Zdroj: Vaccine
ISSN: 1873-2518
0264-410X
Popis: Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.
Databáze: OpenAIRE
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