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.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-02182010-145139 |
| Date | 04 March 2010 |
| Creators | McBurney, Sean Patrick |
| Contributors | Karen Norris, Ted Ross, Todd Reinhart, Penelope Morel, Kelly Stefano Cole, Ronald Montelaro |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-02182010-145139/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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