Rapid development of optimized recombinant adenoviral vaccines for biosafety level 4 viruses

• Main Author: Sahib, Mickey M.
• Other Authors: Kobinger, Gary (Medical Microbiology)
• Language: en_US
• Published: 2010
• Subjects: Crimean; Rift Valley; Nipah; vaccine; immunity; adenovirus
• Online Access: http://hdl.handle.net/1993/4135

This thesis describes the production of adenovirus-based vaccines containing codon-optimized genes from Nipah virus and Crimean-Congo Hemorrhagic Fever virus. Genes encoding envelope proteins from Crimean-Congo Hemorrhagic Fever Virus and Nipah Virus were codon-optimized for translation in human cells and constructed using a modified method of non-gapped gene synthesis, while the entire M segment encoding the glycoprotein precursor for Crimean-Congo Hemorrhagic Fever Virus was commercially synthesized. Genes were cloned into recombinant human adenovirus serotype 5 and the resulting viral particles were amplified, titred and analyzed for in vivo efficacy. Results show that a modified method of non-gapped gene synthesis is an effective and efficient method of producing antigen-encoded DNA and at a fraction of the cost and time required for commercial synthesis. Furthermore, adenovirus-based vaccines induce both cellular and humoral immune responses providing for a highly efficacious vaccine during potential disease outbreaks, where time to completion is of utmost importance. This study has shown that recombinant adenoviral vaccines for Crimean-Congo Hemorrhagic Fever virus and Nipah virus can be produced rapidly and efficiently from virtual DNA sequence to optimized recombinant vaccines in just eight months.