Characterization of Neutralizing Sites in the Second Variable and Fourth Variable Region in gp125 and a Conserved Region in gp36 of Human Immunodeficiency Virus Type 2

Skott, Pia; Achour, Adnane; Norin, Martin; Thorstensson, Rigmor; Björling, Ewa

doi:10.1089/vim.1999.12.79

Cited by 9 publications

(12 citation statements)

References 30 publications

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“…Although immune sera raised against a linear peptide derived from the MPER of gp36 and conjugated to a carrier protein have been re- ported to show neutralizing activity [15] , the sera obtained here did not neutralize. Until now there are no reports showing the existence and prevalence of mAb 2F5/4E10-like neutralizing antibodies in HIV-2-infected patients.…”

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confidence: 56%

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Induction of Antibodies Binding to the Membrane Proximal External Region of gp36 of HIV-2

Behrendt

Fiebig²,

Kurth³

et al. 2011

Intervirology

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Objective: The ability to induce neutralizing antibodies may be the most important feature of an antiretroviral vaccine, preventing infection of target cells and subsequent integration of the virus into the cellular genome where the virus may persist. Broadly neutralizing antibodies directed against conserved epitopes in the membrane proximal external region (MPER) of the transmembrane envelope (TM) protein gp41 of HIV-1 such as the monoclonal antibodies (mAb) 2F5 and mAb 4E10 have been found in infected individuals; however, all attempts to induce such antibodies failed. In individuals infected with HIV-2 such antibodies were not yet reported. Methods: Two recombinant proteins corresponding to the ectodomain of the TM protein gp36 of HIV-2 were produced, rats were immunized and sera were analyzed for binding and neutralizing antibodies. Results: Although binding antibodies were induced, none of the sera neutralized HIV-2. Most interestingly, epitope mapping showed specific binding of the antibodies to the MPER of gp36, to a region homologous to the binding site of the mAb 4E10 in gp41 of HIV-1. Conclusions: Although MPER-specific antibodies were induced by vaccination with gp36, these antibodies did not neutralize HIV-2. This is similar to the situation with HIV-1, but in contrast to that with gammaretroviruses.

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mentioning

confidence: 56%

“…results]. To our knowledge, there is no information about mAb 2F5/4E10-like neutralizing antibodies in patients infected with HIV-2 and only a few attempts have been undertaken to induce such antibodies [15] .…”

mentioning

confidence: 99%

Induction of Antibodies Binding to the Membrane Proximal External Region of gp36 of HIV-2

Behrendt

Fiebig²,

Kurth³

et al. 2011

Intervirology

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“…The V1, V2 and V4 Env variable loops can also serve as targets for neutralizing antibodies to HIV-1 Env [97][98][99][100][101][102]. Similar to the V3 loop antibody repertoire, many of the V1, V2 and V4 specifities of induced antibodies are strain specific.…”

Section: Antibody Escape and Evasion Mechanisms Of Hiv-1mentioning

confidence: 99%

“…However, one goal of vaccine development is to find antibody specificities that can bind to native Env trimers and induce the exposure of critical epitopes on the V3 loop. V3 immunogens that reflect conserved functional regions of the V3 loop would then become viable vaccine targets.The V1, V2 and V4 Env variable loops can also serve as targets for neutralizing antibodies to HIV-1 Env [97][98][99][100][101][102]. Similar to the V3 loop antibody repertoire, many of the V1, V2 and V4 specifities of induced antibodies are strain specific.…”

mentioning

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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“…They have been identified in V1, V2, V3, V4 and C5 regions, and in the CD4-binding site [19,21,23,26-29]. These epitopes are well exposed in the envelope complex of CCR5-using isolates that are usually highly sensitive to antibody neutralization [21,27].…”

Section: Introductionmentioning

confidence: 99%

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

et al. 2013

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BackgroundDifferently from HIV-1, HIV-2 disease progression usually takes decades without antiretroviral therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth.ResultsCD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies.ConclusionOur data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs play an important role in HIV-2 pathogenesis.

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Characterization of Neutralizing Sites in the Second Variable and Fourth Variable Region in gp125 and a Conserved Region in gp36 of Human Immunodeficiency Virus Type 2

Cited by 9 publications

References 30 publications

Induction of Antibodies Binding to the Membrane Proximal External Region of gp36 of HIV-2

Induction of Antibodies Binding to the Membrane Proximal External Region of gp36 of HIV-2

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

Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

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