Date Degree Awarded

Summer 7-31-2019

Degree Type

Restricted to Claremont Colleges Dissertation

Degree Name

PHD in Applied Life Sciences

First Thesis/Dissertation Advisor

Larry Grill

Second Thesis/Dissertation Advisor

Mikhail Martchenko

Third Thesis/Dissertation Advisor

Craig Adams

Terms of Use & License Information

Terms of Use for work posted in Scholarship@Claremont.

Abstract

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of ZIKV-specific neutralizing antibodies that may have applications in therapeutics and diagnostics. In the second study, anthrax toxin domains were expressed, purified, and conjugated to the outer surface of modified TMV nanoparticles. These VNPs were readily recognized by anthrax immune serum, but further studies will be necessary to ascertain their ability to induce a protective immune response. As demonstrated in these studies, genetic fusions and chemical conjugations to TMV each have distinct benefits and limitations. However, both methods result in the production of TMV-based VNPs, in which the TMV virion acts as both a scaffold and delivery mechanism, ensuring that the foreign antigens are taken up by DCs, transported to lymph nodes, and stimulate robust, antigen-specific B and T cell responses. In summation, this work shows how TMV VNPs displaying exogenous antigens can be used to create novel vaccines against both viral and bacterial pathogens.

Rights Information

© 2019 Elizabeth A. Henderson

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