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Development of Broadly Reactive HIV-1/AIDS Virus-like Particle Vaccines

McBurney, Sean Patrick (2010) Development of Broadly Reactive HIV-1/AIDS Virus-like Particle Vaccines. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The vast diversity of HIV-1 infections has greatly impeded the development of a successful HIV-1/AIDS vaccine. Previous vaccine work has demonstrated limited levels of protection against SHIV/SIV infection, but protection was only observed when the challenge virus was directly matched to the vaccine strain. As it is likely impossible to directly match the vaccine strain to all infecting strains in nature, it is necessary to develop an HIV-1 vaccine that can protect against a heterologous viral challenge. Envelope-based vaccines were developed containing gp120 monomers, gp140 trimers and gp160 on the surface of a virus-like particle. Vaccination studies indicated that similar systemic levels of Env-specific antibodies were generated by each vaccine. However the VLP-based vaccine led to increased recognition of Env epitopes as well as a significant increase in mucosal Env antibody responses. Also the VLP-based vaccine led to the development of strong cellular responses to both Env and Gag. Therefore the VLP platform was moved forward to develop broadly reactive vaccines. Consensus and Polyvalent clade B and clade C vaccines were developed and investigated for cellular responses in mice. The results indicated that both Polyvalent and Consensus VLP vaccines led to an increase in the number of cellular Env epitopes recognized as compared with primary Envelope-based vaccines. These findings were true for both clade B and clade C vaccines. To determine the level of protection generated by VLP based vaccines, consensus clade B as well as a polyvalent clade B vaccine were investigated in non-human primates. The polyvalent clade B vaccine led to the protection of 3 out of 4 challenged animals with decreased viral burden observed in the infected individual. Overall these studies indicate that a virus-like particle vaccine encoding multiple primary envelopes is a promising HIV-1/AIDS vaccine strategy for protecting against heterologous HIV-1 viruses.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
McBurney, Sean Patrickspm10@pitt.eduSPM10
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRoss, Tedtmr15@pitt.eduTMR15
Committee MemberNorris, Karenkan1@pitt.eduKAN1
Committee MemberStefano Cole, Kellystefcole@pitt.eduSTEFCOLE
Committee MemberMorel, Penelopemorel@pitt.eduMOREL
Committee MemberMontelaro, Ronaldrmont@pitt.eduRMONT
Committee MemberReinhart, Toddreinhar@pitt.eduREINHAR
Date: 4 March 2010
Date Type: Completion
Defense Date: 27 January 2010
Approval Date: 4 March 2010
Submission Date: 18 February 2010
Access Restriction: 5 year -- Restrict access to University of Pittsburgh for a period of 5 years.
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Molecular Virology and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: consensus; HIV-1 vaccine; polyvalent; virus-like particle
Other ID:, etd-02182010-145139
Date Deposited: 10 Nov 2011 19:31
Last Modified: 15 Nov 2016 13:36


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