Identifying epitopes of HIV-1 that induce protective antibodies

Zolla‐Pazner, Susan

doi:10.1038/nri1307

Cited by 291 publications

(276 citation statements)

References 131 publications

(161 reference statements)

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“…Recently, two reports have described selection of anti-gp41 antibodies by using gp41 fragments for panning of phage antibody libraries but the selected antibodies exhibited relatively modest neutralizing activity (Louis et al, 2005;Miller et al, 2005). These results are consistent with the findings that the use of gp41 fragments that contain exposed antibodyaccessible surfaces and resemble some fusion intermediates or post-fusion structure as vaccine immunogens leads to elicitation of weakly neutralizing antibodies or antibodies lacking broadly neutralizing activity against primary isolates (Zolla-Pazner, 2004b). …”

Section: Introductionsupporting

confidence: 78%

“…As a result, elicitation of cross-reactive neutralizing antibodies in vivo is rareand usually occurs after relatively long periods of maturation (Burton et al, 1997) (Zolla-Pazner, 2004a). Only several Env-specific hmAbs have been identified (Zolla-Pazner, 2004a) that exhibited neutralizing activity to primary isolates from different clades including the anti-gp120 human monoclonal antibodies b12 Roben et al, 1994), 2G12 (Trkola et al, 1996;Sanders et al, 2002;Scanlan et al, 2002), m14 (Zhang et al, 2004b), m18 , F105 ( ?…”

Section: Introductionmentioning

confidence: 99%

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Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

Zhang

Choudhry

Sidorov

et al. 2006

Journal of Immunological Methods

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The HIV envelope glycoprotein (Env) is composed of two non-covalently associated subunits: gp120 and gp41. Panning of phage-displayed antibody libraries against Env-based antigens has resulted mostly in selection of anti-gp120 antibodies. Native gp41 in the absence of gp120 is unstable. The use of gp41 fragments as antigens has resulted in selection of antibodies with relatively modest neutralizing activity. To enhance selection of antibodies specific for gp41 in the context of the whole Env we have developed a methodology termed competitive antigen panning (CAP). By using CAP we identified a novel gp41-specific human monoclonal antibody (hmAb), m48, from an immune library derived from long-term nonprogressors with high titers of broadly cross-reactive neutralizing antibodies (bcnAbs). M48 was only selected by CAP but not by the conventional preincubation methodology. It neutralized a panel of HIV-1 primary isolates from different clades in assays based on spreading infection in peripheral blood mononuclear cells (PBMCs) with potency higher than that of the well characterized broadly cross-reactive HIV-1-neutralizing antibodies IgG1 4E10 and Fab Z13. These results may have implications for selection of novel gp41-specific bcnAbs, and for the development of HIV-1 inhibitors and vaccine immunogens.

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Section: Introductionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

Zhang

Choudhry

Sidorov

et al. 2006

Journal of Immunological Methods

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“…During the natural course of HIV infection, fully functional variants continuously emerge and compete for outgrowth in the presence of a rapidly evolving neutralizing Ab response, which exerts a high level of selective pressure. Non-neutralizing epitopes, which are usually very conserved, could also be the targets of immune intervention (10,12). In that respect, the sharp conservation of the 3S-motif among all viral isolates (6) suggests that 3S-based peptides provide a major B-cell epitope that should be considered for use to limit virus pathogenicity, independently of pathogen replication.…”

mentioning

confidence: 99%

A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 ⁺ T cell depletion in SHIV-infected macaques

Vieillard

Grand

Dausset

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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We previously showed that a gp41 peptide (3S) induces expression of a natural killer (NK) ligand (NKp44L) on CD4 ؉ T cells during HIV-1 infection and that those cells are highly sensitive to NK lysis. In HIV-infected patients, anti-3S antibodies are associated with the maintenance of CD4 ؉ T cell counts close to their baseline values, and CD4 ؉ T cells decrease with the antibody titer. This study sought to determine whether anti-3S immunization could prevent NKp44L expression on these CD4 ؉ T cells in vivo and inhibits the subsequent decline in CD4 ؉ T cell counts by immunizing macaques with 3S and then infecting them with simian HIV162P3. The results show that anti-3S antibodies inhibited NKp44L expression and NK activity and cytotoxicity. They also decreased the apoptosis rate of CD4 ؉ T cells in peripheral blood and lymph nodes. These data raise questions about the pathogenesis of HIV and present opportunities for both preventive and therapeutic HIV vaccine strategies.

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“…The ELDKWA epitope seems to be a potential target for neutralization by Abs (27), but, elicitation of Abs against it, especially mucosal Abs with transcytosis and infection neutralizing activities, has proved difficult and reported successes are scant (27,28). Here, we explore the potential of a chimeric protein comprised of the P1 peptide fused to the G M1 -ganglioside-binding B subunit of the cholera toxin (CTB) to fulfill the requirements of contextual integrity of this gp41 domain, mucosal targeting, and immunogenicity.…”

mentioning

confidence: 99%

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

Matoba

Magérus

Geyer

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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A vaccine that would engage the mucosal immune system against a broad range of HIV-1 subtypes and prevent epithelial transmission is highly desirable. Here we report fusing the mucosal targeting B subunit of cholera toxin to the conserved galactosylceramide-binding domain (including the ELDKWA-neutralizing epitope) of the HIV-1 gp41 envelope protein, which mediates the transcytosis of HIV-1 across the mucosal epithelia. Chimeric protein expressed in bacteria or plants assembled into oligomers that were capable of binding galactosyl-ceramide and G M1 gangliosides. Mucosal (intranasal) administration in mice of the purified chimeric protein followed by an i.p. boost resulted in transcytosis-neutralizing serum IgG and mucosal IgA responses and induced immunological memory. Plant production of mucosally targeted immunogens could be particularly useful for immunization programs in developing countries, where desirable product traits include low cost of manufacture, heat stability, and needle-free delivery.

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Identifying epitopes of HIV-1 that induce protective antibodies

Cited by 291 publications

References 131 publications

Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 ⁺ T cell depletion in SHIV-infected macaques

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

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Identifying epitopes of HIV-1 that induce protective antibodies

Cited by 291 publications

References 131 publications

Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

Selection of a novel gp41-specific HIV-1 neutralizing human antibody by competitive antigen panning

A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 + T cell depletion in SHIV-infected macaques

A mucosally targeted subunit vaccine candidate eliciting HIV-1 transcytosis-blocking Abs

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A vaccine strategy against AIDS: An HIV gp41 peptide immunization prevents NKp44L expression and CD4 ⁺ T cell depletion in SHIV-infected macaques