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Journal of Virology, August 2005, p. 10210-10217, Vol. 79, No. 16
0022-538X/05/$08.00+0 doi:10.1128/JVI.79.16.10210-10217.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
Departments of Medicine,1 Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA,2 UCLA AIDS Institute,3 Department of Medicine, VA Greater Los Angeles Healthcare System, Los Angeles, California4
Received 3 January 2005/ Accepted 4 May 2005
The lack of success of subunit human immunodeficiency virus (HIV) type 1 vaccines to date suggests that multiple components or a complex virion structure may be required. We hypothesized that the failure of current vaccine strategies to induce protective antibodies is linked to the inability of native envelope structures to readily elicit these types of antibodies. We have previously reported on the ability of a formaldehyde-treated, heat-inactivated vaccine to induce modest antibody responses in animal vaccine models. We investigated here whether immunization for HIV with an envelope-modified, formaldehyde-stabilized, heat-inactivated virion vaccine could produce higher-titer and/or broader neutralizing antibody responses. Thus, a clade B vaccine which contains a single point mutation in gp41 (Y706C) that results in increased incorporation of oligomeric Env into virions was constructed. This vaccine was capable of inducing high-titer antibodies that could neutralize heterologous viruses, including those of clades A and C. These results further support the development of HIV vaccines with modifications in native Env structures for the induction of neutralizing antibody responses.
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