Evaluation of the Efficacy of a Recombinant Simian Varicella Virus Vaccine Expressing Simian Immunodeficiency Virus Envelope and Capsid Proteins

Wichman, Thomas G (2019) Evaluation of the Efficacy of a Recombinant Simian Varicella Virus Vaccine Expressing Simian Immunodeficiency Virus Envelope and Capsid Proteins. Undergraduate thesis, under the direction of Wayne L. Gray from Biological Sciences, The University of Mississippi.

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Abstract

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T-lymphocytes, which when left untreated, later develops into Acquired Immunodeficiency Syndrome (AIDS). Up to 25,000 people die every week from AIDS infection, making HIV and AIDS research a very high priority for virologists. While highly researched by scholars around the world, no person has been able to develop a successful vaccine, as the retroviral nature of the virus and its high mutation rate make vaccine development incredibly difficult. However, recombinant genetic technology will hopefully allow the revolutionization of vaccines which have already proven effective in immunization. The already developed varicella-zoster virus (VZV) vaccine’s safety, effectiveness, and infection range limited to humans make it a great vector for the creation of a recombinant HIV Vaccine. In this study, simian varicella virus (SVV) and simian immunodeficiency virus (SIV) act as a model to evaluate a recombinant vaccine’s effectiveness on non-human primates’ humoral responses. The wide-scale goal of HIV and concurrent AIDS and SIV research is to both cure and prevent these diseases; in the research this thesis follows, the aim is to create a recombinant SVV vaccine which can manifest immunity in non-human primates, with hopes to parallel that research for a similar vaccine for human use. The specific aims of this thesis include: the development of an optimal protocol for antibody response analysis, and the evaluation of the efficacy of a recombinant SVV vaccine expressing SIV gag and env proteins, either with a protein boost or a DNA boost. After the protocol was modified and optimized, sera from rhesus macaques at different points throughout their immunization schedules were analyzed via western blot. Results showed that the prime-boost schedule is effective in inducing an antibody-mediated response, specifically after boosting, and that a protein vaccine boost rather than DNA vaccine boost is the most effective. This model will continue to be researched further in hopes of developing a successful SIV, and subsequently, HIV vaccine.

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