Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers

Belshe, Robert B.; Gorse, Geoffrey J.; Mulligan, Mark J.; Evans, Thomas G.; Keefer, Michael C.; Excler, Jean–Louis; Duliegè, Anne-Marie; Tartaglia, James; Cox, William I.; McNamara, James; Hwang, Kai; Bradney, Alice; Montefiori, David C.; Weinhold, Kent J.

doi:10.1097/00002030-199818000-00009

Cited by 157 publications

(101 citation statements)

References 17 publications

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“…Subunit proteins alone have elicited high titers of neutralizing antibodies against TCLA strains, where a minimum of three to four inoculations generally achieves peak titers [32][33][34][35][36]. Peak responses with recombinant pox-virus vectors have been lower, but can increase dramatically after one or two subunit protein boosts [37][38][39][40][41][42], suggesting effective B-cell priming by the vectored immunogen. Similar secondary neutralizing antibody responses are observed post-AIDS virus infection in macaques that are previously immunized with recombinant Env-containing DNA and viral vectors [43][44][45][46][47][48][49].…”

Section: Hiv-1 Immunogensmentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

104

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Neutralizing antibody induction is a key feature of many effective vaccines and is the only immune response that has proven to be capable of completely blocking AIDS virus infection in animal models. Unfortunately, the extensive genetic variability and complex immune-evasion strategies of HIV-1 have thwarted all attempts to date at eliciting an effective neutralizing antibody response with candidate HIV-1 vaccine immunogens. Recent advances in our understanding of how these evasion strategies operate, coupled with growing progress in unravelling the structure and immunobiology of the viral envelope glycoproteins, are contributing to novel immunogen designs to overcome the many barriers to inducing protective antibodies against HIV-1. Keywordsantiretroviral therapy; HIV-1; host cell fusion; immunogen; neutralizing antibody induction Development of a safe, practical and effective HIV-1 vaccine is one of the highest priorities of the global scientific community [1,2]. Although antiretroviral therapy (ART) has dramatically prolonged the lives of HIV-1 infected patients, ART is not yet routinely available in developing countries, and the global rate of spread of HIV-1 continues unabated. If no effective AIDS vaccine is developed by 2010, the number of people infected world-wide with HIV-1 could exceed 60 million [3].In spite of more than 20 years of research, the types of immune responses needed to protect an immunized individual from HIV-1 infection are not known. Its is known that CD8 + cytotoxic T-cell responses can control HIV-1 replication to varying degrees in acute HIV-1 infection (AHI) [4,5], and when induced by immunogens, can control viral set point after simian immunodeficiancy virus (SIV) or simian HIV (SHIV) challenges in non-human primates [4]. Strong proliferative CD4 + T-cell responses to HIV-1 proteins have been demonstrated to correlate well with immune control of HIV-1 viral load [5]. Therefore, it is highly desirable for an HIV-1 vaccine co induce robust CD4 + and CD8 + T-cell responses in order to control virus replication and reduce the likelihood of subsequent transmission [4][5][6][7]. The potential for complete ('sterilizing') immunity from HIV-1 infection may depend on the presence of pre-existing neutralizing antibodies. We know that neutralizing antibodies can prevent the acquisition of AIDS virus infection after intravenous, vaginal, rectal and oral virus challenge in nonhuman primates [8][9][10][11][12]. This level of protection is highly attractive for a vaccine against a virus, such as HIV-1, which integrates genetically and forms latent viral reservoirs soon after infection. However, the diversity of transmitted HIV-1 genetic variants and the relative resistance of the majority of HIV-1 primary isolates to most types of inducible neutralizing antibodies have posed major hurdles to current vaccine efforts. Furthermore, the few rare broadly reactive neutralizing monoclonal antibodies (mAbs) that have been isolated from HIV-1 infected patients represent species of antibodies that...

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Section: Hiv-1 Immunogensmentioning

confidence: 99%

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Haynes¹,

Montefiori²

2006

Expert Review of Vaccines

104

View full text Add to dashboard Cite

show abstract

“…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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“…This problem has led to speculation that vaccine-induced T cell responses alone might be sufficient for protection (22,23). There has been some success in generating CD8 ϩ T cell responses by prototype vaccines both in experimental animals and in phase I clinical trials (24)(25)(26)(27), but T cell-based vaccines have not provided sterilizing immunity.…”

mentioning

confidence: 99%

Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection

Messer

Dittmer

Peterson

et al. 2004

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

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Induction of immune responses to HIV-1 by canarypox virus (ALVAC) HIV-1 and gp120 SF-2 recombinant vaccines in uninfected volunteers

Abstract: The live canarypox vector was safe, stimulated cytotoxic T-cells and primed for a vigorous neutralizing antibody response upon boosting with subunit gp120 vaccine. This vaccine combination should be evaluated further for inducing protection against HIV infection.

Cited by 157 publications

References 17 publications

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

Aiming to induce broadly reactive neutralizing antibody responses with HIV-1 vaccine candidates

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

Essential role for virus-neutralizing antibodies in sterilizing immunity against Friend retrovirus infection

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