Formaldehyde-treated, heat-inactivated virions with increased human immunodeficiency virus type 1 env can be used to induce high-titer neutralizing antibody responses.
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.
Poon
B
B
Department of Medicine, David Geffen School of Medicine at UCLA, 11-934 Factor Building, Los Angeles, CA 90095, USA.
Hsu
J F
JF
Gudeman
V
V
Chen
I S Y
IS
Grovit-Ferbas
K
K
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D005260:Female; D005557:Formaldehyde / Q000494:pharmacology*; D015483:HIV Antibodies / Q000097:blood*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011817:Rabbits; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D014771:Virion / Q000276:immunology*
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D015164:Vaccines, Inactivated; D005557:Formaldehyde