Date of Award

2019

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Cell & Molecular Biology

First Advisor

David B. Weiner

Abstract

Vaccines against oncogenic viruses such as human papillomavirus and hepatitis B have decreased the incidence of these infections and the cancers that result from them. Epstein-Barr virus (EBV) is an enveloped gammaherpesvirus that has been linked to cancers such as Burkitt lymphoma, Hodgkin’s lymphoma, gastric carcinoma, and nasopharyngeal carcinoma, as well as autoimmune diseases that include multiple sclerosis and systemic lupus erythematosus. It infects over 90% of the adult population globally. Initial infection is often subclinical, but it can present acutely as infectious mononucleosis, with symptoms that can last from weeks to months, especially in adolescents and young adults. DNA immunogens targeting EBV were developed to drive cellular and humoral immunity against viral antigens, and these immune responses were able to protect against the infection of human cells, as well as limit the growth of antigen-expressing cancer in mice. Viral latent proteins and glycoproteins were made into novel vaccines using their synthetic conserved sequences encoded within plasmids and administered using electroporation. EBV latent protein DNA immunogens elicited potent cellular responses and inhibited the growth of tumors that expressed latent membrane protein 2 (LMP2). DNA immunogens developed against EBV glycoproteins also generated strong cellular responses and produced antibodies to their cognate antigens, with mouse sera drawn after vaccinations targeting gp350 and gp42 able to block the infection of human B cells. DNA technologies that combine multiple immunogens of EBV into novel vaccination formulations may produce the immune responses necessary to limit this infectious disease and the cancers associated with it. These vaccines have the potential to impact the significant morbidity that results from infection and the roughly 1.5% share of the global cancer burden that is associated with EBV.

Embargoed

Available to all on Saturday, May 11, 2024

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