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Title: Developing a new generation of Modified Vaccinia Ankara Vector to develop vaccines for emerging infectious diseases (single dose) as well as cancer

Farshad Guirakhoo

Chief Scientific Officer GeoVax, Inc., USA

Biography

Dr. Guirakhoo is CSO at GeoVax and was named one of the ‘50 Most Influential People in Vaccines’ in Vaccine Nation’s 2014 list. His previous assignments were CTO at Vaxess, CSO at Hookipa Biotech and Executive Director of External R&D at Sanofi Pasteur. He co-invented the ChimeriVax™ technology platform in association with St. Louis University which resulted in commercial products for dengue, JE and WN. Dr. Guirakhoo holds a BSc in Biology, a MSc in genetics, and a PhD in Virology. Dr. Guirakhoo has filed for more than 200 patents, 20 issued and published 90 papers in peer reviewed scientific journals including 13 book chapters.

Abstract

Background: Single-dose protection is a favourable characteristic of a vaccines for emerging infectious disease outbreak response, given the speed of spread of pathogens and the impracticality of multi-dose regimens in the under-resourced settings where outbreaks often occur. 
We have utilized our 5th generation MVA vector platform, that is improved for high expression and stable transgenes during manufacture, to develop single dose vaccines for Zika, Ebola, and Lassa fever viruses. The MVA virus has the advantages of being a live replication-competent vector in avian cells for manufacturing purposes, yet replication-deficient in mammalian cells for vaccination, thus inherently safe.  Importantly, MVA vaccines elicit protective T cell as well as long lasting antibody responses in animals and humans. The MVA platform can be combined with the potent immunogenicity of Virus Like Particles (VLPs) or be used to express proteins in their native conformations enabling vaccines that induce full protection after a single dose. The safety and immunogenicity of the platform was first validated in animal and human studies using DNA and MVA-VLP-HIV vaccines and further expanded for developing vaccine candidates against emerging pathogens, endemic diseases or even cancer. 

Methods: Vaccine constructs were made using MVA vector technology and fully characterized in vitro (e.g. sequencing, WB, Immunostaining and electron microscopy). For constructions of Ebola and Lassa fever vaccine candidates, two genes from each pathogen were used to generate VLPs; GP+VP40 for Ebola and GPC+Z genes for Lassa fever vaccine. For Zika vaccine NS1 was used as the protective immunogen since this protein is not associated with induction of Antibody Dependent Enhancement of infection (ADE), a potential risk for other Zika vaccines in development.  

Results: In studies for Ebola, Lassa and Zika, a single dose of vaccine generated robust antibody and T cell responses and fully protected animals (rodents and non-human primates) against a lethal challenge.

Conclusion: In this talk, we provide the latest data thon single dose vaccine efficacy, including characterization of humoral and T cell responses, lack of vector immunity and the onset of a protective immune response, for these 3 different pathogens as examples for a broad utility of the platform for other indications.