Date of Award

5-1-2021

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (v, 57 pages) : illustrations (some color)

Dissertation/Thesis Chair

Nicholas Mantis

Committee Members

Christina Egan, Norma Tavakoli, Eric Yager

Keywords

Ricin, Antigenic determinants, Vaccines, Immune response

Subject Categories

Immunology of Infectious Disease

Abstract

Assessing the performance and durability of the antibody response in animal models can assist in the development of biodefense vaccines. Ricin is one of the most toxic biological agents known and has been a public health issue for years. Since ricin is easily manufactured and a deadly toxin, rational vaccine design and immunotherapeutic optimization have been explored. RiVax® is a candidate subunit vaccine with a modified A-chain of ricin toxin that was formulated to remove ricin's biological activity. It is thought that RiVax® could serve as a prophylactic that would induce humoral- and cell-mediated immunological responses that elicit protective antigens against ricin. Since RiVax® could serve as a biodefense vaccine, it was important to assess the performance of RiVax® in conferring durable systemic and mucosal immunity to ricin toxin, especially in a mouse model. We assessed performance and durability using two well established methods, endpoint titer ELISA and epitope profiling immune-competition capture (EPICC) assay, which have served as correlates of protection in animal models. We found that RiVax® produces a durable antibody response that was stable up to a year after two vaccination doses. We also illustrate the importance of multiple vaccination dosages, as we observed that a single dose of RiVax® is not sufficient in providing protection against systemic ricin challenge. Finally, we identified that there was a difference in survival between mice challenged with similar doses through IP or IN route, suggesting that there must be a robust antibody response produced in both systemic and mucosal compartments in order to protect against lethal doses of ricin toxin. Efficacy serves as a priority for vaccine development, but identifying and measuring correlates of protection are essential for the authorization of biodefense vaccines.

Download

Share

COinS