Immunization with Recombinant Canarypox Vectors Expressing Membrane-Anchored Glycoprotein 120 Followed by Glycoprotein 160 Boosting Fails to Generate Antibodies That Neutralize R5 Primary Isolates of Human Immunodeficiency Virus Type 1

Bures, Renata; Gaitan, Alicia; Zhu, Tuofu; Graziosi, Cecilia; McGrath, Kathryn M.; Tartaglia, James; Caudrelier, Pierre; Habib, Raphaëlle El; Klein, Michél R.; Lazzarin, Adriano; Stablein, Donald M.; Deers, Mark; Corey, Lawrence; Greenberg, Michael; Schwartz, David H.; Montefiori, David C.

doi:10.1089/088922200750054756

Cited by 144 publications

(123 citation statements)

References 101 publications

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“…Early efforts in HIV vaccine development focused on the induction of humoral responses by using recombinant Env glycoproteins [2][3][4][5]. The immunogenicity of recombinant Env protein-based vaccines was poor in humans, as shown by overall low-level binding antibodies measured by solid phase assays [6] and by the narrow spectrum of neutralizing activities mainly against T-cell line adapted (TCLA) viral isolates [7][8][9]. Ultimately, recombinant protein-based HIV-1 vaccines failed to show protection efficacy in Phase III clinical trials [10,11].…”

Section: Introductionmentioning

confidence: 99%

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

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124

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An optimally effective AIDS vaccine would likely require the induction of both neutralizing antibody and cell-mediated immune responses, which has proven difficult to obtain in previous clinical trials. Here we report the induction of Human Immunodeficiency Virus Type-1 (HIV-1)-specific immune responses in healthy adult volunteers that received the multi-gene, polyvalent, DNA prime-protein boost HIV-1 vaccine formulation, DP6−001 in a Phase I clinical trial conducted in healthy adult volunteers of both genders. Robust cross-subtype HIV-1-specific T cell responses were detected in IFNγ ELISPOT assays. Furthermore, we detected high titer serum antibody responses that recognized a wide range of primary HIV-1 Env antigens and also neutralized pseudotyped viruses that express the primary Env antigens from multiple HIV-1 subtypes. These findings demonstrate that the DNA prime-protein boost approach is an effective immunization method to elicit both humoral and cellmediated immune responses in humans, and that a polyvalent Env formulation could generate broad immune responses against HIV-1 viruses with diverse genetic backgrounds.

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Section: Introductionmentioning

confidence: 99%

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Wang

Kennedy

West

et al. 2008

Vaccine

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124

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“…In natural infection, antisera that can neutralize a broad spectrum of HIV-1 primary isolates are uncommon and of low titer. Likewise, vaccine sera are generally ineffective against primary isolates (1)(2)(3)(4)(5). The relative resistance of HIV-1 primary isolates seems to be because of a decreased accessibility of the relevant neutralization epitopes on the envelope glycoproteins (6)(7)(8)(9).…”

Section: H Uman Immunodeficiency Virus Type 1 (Hiv-1) Infectionmentioning

confidence: 99%

The role of the third β strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012

Zhu

Holz-Smith

et al. 2001

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

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Neutralization of HIV-1 primary isolates has been a tremendous challenge for AIDS vaccine development. Here, we identify a single amino acid change (T198P) in gp120 that alters the neutralization sensitivity of the primary isolate DH012 to antibodies against multiple neutralization epitopes that include the V3, CD4-induced, and CD4 binding sites in gp120. This mutation is located in the V1͞V2 stem region that forms the third ␤ strand (␤3) of the bridging sheet of gp120. The conformation of variable loops, especially V1͞V2 and V3, was proposed to regulate the accessibility of these neutralization epitopes. The results of this study indicate a direct association between the V1͞V2 and V3 loops of DH012 gp120. The single amino acid mutation T198P in the ␤3 severely compromises the interaction between the V1͞V2 and V3 loops. These results suggest that interaction of V1͞V2 and V3 can mask the neutralization epitopes and that the ␤3 plays a critical role in determining the neutralization sensitivity by modulating the interaction. This study provides an insight into why primary isolates are relatively resistant to antibody neutralization and might facilitate the development of anti-HIV strategies against HIV-1 infection.

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“…As such, it represents an interesting candidate for vaccine immunogen design. However, vaccination trials with Env in soluble or recombinant forms elicited responses with only minimal effectiveness against most primary HIV-1 isolates [1][2][3] . Nonetheless, partial efficacy observed in the RV144 vaccine trial 4 renewed interest in HIV-1 Env as an immunogen candidate.…”

Section: Introductionmentioning

confidence: 99%

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay

Veillette

Coutu

Richard

et al. 2014

JoVE

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HIV-1 envelope glycoproteins (Env) mediate viral entry into target cells and are essential to the infectious cycle. Understanding how those glycoproteins are able to fuel the fusion process through their conformational changes could lead to the design of better, more effective immunogens for vaccine strategies. Here we describe a cell-based ELISA assay that allows studying the recognition of trimeric HIV-1 Env by monoclonal antibodies. Following expression of HIV-1 trimeric Env at the surface of transfected cells, conformation specific anti-Env antibodies are incubated with the cells. A horseradish peroxidase-conjugated secondary antibody and a simple chemiluminescence reaction are then used to detect bound antibodies. This system is highly flexible and can detect Env conformational changes induced by soluble CD4 or cellular proteins. It requires minimal amount of material and no highly-specialized equipment or know-how. Thus, this technique can be established for medium to high throughput screening of antigens and antibodies, such as newly-isolated antibodies. Video LinkThe video component of this article can be found at

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Immunization with Recombinant Canarypox Vectors Expressing Membrane-Anchored Glycoprotein 120 Followed by Glycoprotein 160 Boosting Fails to Generate Antibodies That Neutralize R5 Primary Isolates of Human Immunodeficiency Virus Type 1

Cited by 144 publications

References 101 publications

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers

The role of the third β strand in gp120 conformation and neutralization sensitivity of the HIV-1 primary isolate DH012

Conformational Evaluation of HIV-1 Trimeric Envelope Glycoproteins Using a Cell-based ELISA Assay

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