Year: 2010
Type: article
Abstract: 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.
Author: Sean P. McBurney
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Award: G9000266445
OpenAlex ID: W147113080