Year of Award

2026

Document Type

Thesis

Degree Type

Master of Science (MS)

Other Degree Name/Area of Focus

Toxicology

Department or School/College

College of Health, PBS, Ctr for Environmental Health Sciences

Committee Chair

Blair DeBuysscher, PhD.

Commitee Members

Scott Wetzel, PhD., Brent Ryckman, PhD.

Keywords

MPOX, DESIGN AND PRECLINICAL EVALUATION, ADJUVANTED SUBUNIT, mRNA-LNP VACCINES

Subject Categories

Toxicology

Abstract

Abstract

Over the past four years, the World Health Organization has issued two separate warnings regarding mpox, originally known as the monkeypox virus (MPXV), due to its global proliferation and sustained human-to-human transmission. Currently, the modified vaccinia Ankara (MVA) strain remains the only FDA-approved vaccine; however, while highly similar, it is not specific to MPXV. Consequently, there is an urgent need for vaccines that are tailored to circulating MPXV and adaptable to mutations.

This work evaluated mpox specific adjuvanted subunit and mRNA-LNP vaccines. The lead subunit vaccines contained either M1R or B6R antigen, a combined TLR4 and TLR7/8 agonist as adjuvant and Aluminum hydroxide gel (Alhydrogel). The mRNA-LNP vaccines evaluated different mRNA constructs designed for either intracellular or secreted antigen expression. The immune profile of the vaccine candidates was assessed using a murine model and analysis of antibody titers, effector T-cell cytokine concentrations, and neutralizing antibody responses.

We found that the M1R and B6R adjuvanted subunit and the secreted M1R mRNA-LNP vaccines produced a strong humoral immune response and the wild type (intracellular) M1R mRNA-LNP vaccine that produced a strong humoral and cell mediated immune response. All vaccines elicited immune responses skewed toward an antiviral Th1 dependent profile and M1R TLR4/7/8/Alum subunit vaccine produced antibodies capable of neutralizing MPXV.

Overall, we developed several promising candidate vaccines, as well as potential tools that could be used to help elucidate mpox correlates of protection. Future studies could utilize wild type and secreted mRNA constructs to investigate MPXV correlates of protection, as both constructs elicited a humoral response, but only wild type elicited a robust cell-mediated response.

Available for download on Tuesday, August 01, 2028

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© Copyright 2026 Shaun Michael Jeffery Opp