Magnitude and Breadth of a Nonprotective Neutralizing Antibody Response in an Efficacy Trial of a Candidate HIV-1 gp120 Vaccine

Vaccine Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 08/2010; 202(4):595-605. DOI: 10.1086/654816
Source: PubMed


A candidate vaccine consisting of human immunodeficiency virus type 1 (HIV-1) subunit gp120 protein was found previously to be nonprotective in an efficacy trial (Vax004) despite strong antibody responses against the vaccine antigens. Here we assessed the magnitude and breadth of neutralizing antibody responses in Vax004.
Neutralizing antibodies were measured against highly sensitive (tier 1) and moderately sensitive (tier 2) strains of HIV-1 subtype B in 2 independent assays. Vaccine recipients were stratified by sex, race, and high versus low behavioral risk of HIV-1 acquisition.
Most vaccine recipients mounted potent neutralizing antibody responses against HIV-1(MN) and other tier 1 viruses. Occasional weak neutralizing activity was detected against tier 2 viruses. The response against tier 1 and tier 2 viruses was significantly stronger in women than in men. Race and behavioral risk of HIV-1 acquisition had no significant effect on the response. Prior vaccination had little effect on the neutralizing antibody response that arose after infection.
Weak overall neutralizing antibody responses against tier 2 viruses is consistent with a lack of protection in this trial. The magnitude and breadth of neutralization reported here should be useful for identifying improved vaccines.

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Available from: David C Montefiori, Apr 11, 2014
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    • "However, similar to previous human immunizations with envelope monomers or trimmers, no (broadly) neutralizing antibodies were induced. In the best of the cases, earlier studies showed vaccine-induced antibodies able to neutralize easily neutralizable viral isolates or the vaccine strain only [18-21]. These limitations highlight the need for the design of novel immunogens to elicit broadly neutralizing antibodies, although difficulties related to masked epitopes or tolerance mechanisms induced by self-homologies, among others, remain [22-24]. "
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    • "postulated to induce neutralizing antibodies (Flynn et al., 2005; Pitisuttithum et al., 2006; Gilbert et al., 2010), the prospects for a neutralizing antisera-inducing HIV vaccine appeared bleak and there was a shift within the HIV prevention field toward vaccines designed to induce mainly T cell responses, as previously reviewed (Barouch, 2010; McElrath and Haynes, 2010; Pantaleo et al., 2010; Picker et al., 2012). "
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    • "The gp120 protein component in all 3 clinical trials was designed to elicit NAbs [20, 21]. In Vax004, strong NAb responses were seen against a subset of tier 1 viruses, and sporadic weak responses were seen against tier 2 viruses [22]. Here we assessed the magnitude and breadth of NAb responses in RV144 and Vax003. "
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