The Developmental Process for Adenoviral Vectored Canine Influenza Vaccines

Authors

Nicholas Jeanjaquet, University of Nebraska-LincolnFollow

First Advisor

Eric A. Weaver

Date of this Version

12-2023

Citation

Presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Master of Science

Major: Biological Sciences

Under the supervision of Professor Eric A. Weaver

Lincoln, Nebraska, December 2023

Comments

Copyright 2023, Nicholas Jeanjaquet. Used by permission

Abstract

Canine Influenza Virus (CIV) is a recently emerged branch of Influenza A virus that is highly infectious in dogs. The first strain was isolated in 2003, and it has quickly become endemic in areas with dense dog populations, most notably in Asia. The proximity of dogs to humans, along with their potential to serve as mixing vessels for reassortment, raises concern for possible zoonotic transmission and a potential human pandemic. Available vaccines are not frequently updated and struggle to prevent the spread of currently circulating strains. This highlights the need for a new and more effective vaccine. We outline the developmental process for our proposed solution to providing a more broadly protective vaccine. Initial development began by generating a computationally derived mosaic CIV hemagglutinin (CanH3 Mosaic), designed to maximize potential T cell epitopes. Delivery of this mosaic immunogen will be achieved with both human Adenovirus Type 5 (HAd5) and Canine Adenovirus Type 2 (CAV-2) vectors. Utilizing the pAdEasy vector system, our CanH3 mosaic was cloned into replication-defective HAd5. Simultaneously, we developed a series of plasmids through Gibson assembly and overlapping PCR that can potentially be used to generate recombinant CAV-2. We predict that these adenovirus vectored vaccines, delivering our mosaic immunogen, will be able to provide broader and more durable protection than commercially available vaccines.

Advisor: Eric A. Weaver