DNA-Launched Vaccines for Emerging and Re-emerging Viral Pathogens

Given the large number and increasing frequency of viral outbreaks around the globe, there is a need to address the availability, consistency, and production of vaccines. Although there are approved vaccines for some of these diseases there are still issues that face the implementation of these vaccines is susceptible populations in endemic areas. To address these issues, it was necessary to develop and implement an efficacious, and cost-effective vaccine platform that will elicit strong immune responses when compared to currently approved vaccines. We have developed a rapidly adaptable DNA platform to which previously established, licensed vaccines can be converted, or new vaccines can be developed around. Our DNA-launched vaccine platforms provide a foundation for the additional development of live-attenuated vaccines (LAV) and novel subunit vaccines. For DNA-launched LAVs, the in vitro launched viral particles behave consistently with previous studies. With direct in vivo launch of LAVs from this DNA platform, we are able to achieve similar immune responses in immune deficient mice and superior immune responses in immune-competent mice as traditional methods of LAV vaccination. The in vivo launch of our DNA-based LAVs had a better safety profile than direct injection of in vitro rescued viral particles rescued from the same plasmid. The in vivo electroporation of DNA based LAVs elicits an immune response that can protect mice from a high-dose lethal challenge. We also developed a DNA-launched replicon-based subunit vaccine that can elicit strong immune responses after vaccination and is able to completely prevent infection in mice after a two-dose vaccination regiment. The DNA-launched subunit vaccine is able to decrease infection after a single dose however cellular immunity is increased after mice are given the boost dose. These DNA-launched vaccines can combine the benefits of storage, development, and manipulation of DNA, while increasing the immunogenicity, safety profiles of LAVs and subunit vaccines. These DNA-launched vaccines warrant further consideration for increased testing and evaluation in pre-clinical and clinical trials.

Name thesis:degree_name

Microbiology and Immunology (Doctoral)

Grantor

The University of Texas Medical Branch at Galveston

Year dc:date.issued

2021

Author dc:creator

• Muruato, Antonio

• Biology, Microbiology

Handle dc:identifier.uri

https://hdl.handle.net/2152.3/12483

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/12483