Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model

Gruell, Henning; Bournazos, Stylianos; Ravetch, Jeffrey V.; Ploß, Alexander; Nussenzweig, Michel C.; Pietzsch, John

doi:10.1128/jvi.00868-13

Cited by 24 publications

(14 citation statements)

References 85 publications

(95 reference statements)

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“…Antibodies hold great promise for HIV-1 prophylaxis because they can prevent infection in pre-clinical models even at low concentrations (Gautam et al, 2016; Gruell et al, 2013; Klein et al, 2012; Mascola et al, 2000; Moldt et al, 2012; Shibata et al, 1999; Shingai et al, 2013). Moreover, broad and potent antibodies to HIV-1 develop in a fraction of infected individuals suggesting that such antibodies might also be elicited by vaccination (Burton and Hangartner, 2016; Haynes and Montefiori, 2006; Hraber et al, 2014; Klein et al, 2013b; Mascola and Haynes, 2013; McCoy and Weiss, 2013; West et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice

Escolano

Steichen

Dosenovic

et al. 2016

Cell

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290

346

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Summary A vaccine that elicits broadly neutralizing antibodies (bNAbs) against HIV-1 is likely to be protective, but this has not been achieved. To explore immunization regimens that might elicit bNAbs, we produced and immunized mice expressing the predicted germline of PGT121, a bNAb specific for the V3-loop and surrounding glycans on the HIV-1 spike. Priming with an epitope modifiied immunogen designed to activate germline antibody-expressing B cells, followed by ELISA-guided boosting with a sequence of directional immunogens, native-like trimers with decreasing epitope modification, elicited heterologous tier-2 neutralizing responses. In contrast, repeated immunization with the priming immunogen did not. Antibody cloning confirmed elicitation of high levels of somatic mutation and tier-2 neutralizing antibodies resembling the authentic human bNAb. Our data establishes that sequential immunization with specifically designed immunogens can induce high levels of somatic mutation and shepherd antibody maturation to produce bNAbs from their inferred germline precursors.

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Section: Discussionmentioning

confidence: 99%

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice

Escolano

Steichen

Dosenovic

et al. 2016

Cell

Self Cite

290

346

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“…Antibodies can prevent HIV-1 infection in mice and chimpanzees, and SHIV infection in macaques (Balazs et al, 2012; Bar-ouch et al, 2013; Gruell et al, 2013; Prince et al, 1991; Safrit et al, 1993; Shingai et al, 2013), but attempts to produce effective HIV-1 vaccines by eliciting neutralizing antibodies have been disappointing to date (McCoy and Weiss, 2013). However, the vaccine strategies that were tested did not take into account the recent discovery of naturally arising broad and potent anti-HIV neutralizing antibodies.…”

Section: Perspectives For Antibody-based Vaccines and Therapymentioning

confidence: 99%

Structural Insights on the Role of Antibodies in HIV-1 Vaccine and Therapy

West

Scharf

Scheid

et al. 2014

Cell

316

350

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Despite 30 years of effort, there is no effective vaccine for HIV-1. However, antibodies can prevent HIV-1 infection in humanized mice and macaques when passively transferred. New single-cell-based methods have uncovered many broad and potent donor-derived antibodies, and structural studies have revealed the molecular bases for their activities. The new data suggest why such antibodies are difficult to elicit and inform HIV-1 vaccine development efforts. In addition to protecting against infection, the newly identified antibodies can suppress active infections in mice and macaques, suggesting they could be valuable additions to anti-HIV-1 therapies and to strategies to eradicate HIV-1 infection.

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“…The viral evasion mechanisms used to overcome restriction are highly adapted to the human host and often ineffective in rodent cells. Despite all these difficulties, current transgenic small animal models are sufficiently robust to test the in vivo efficacy of potential antivirals 44,46,50 .…”

Section: Model Systems For Integrative Analyses Of Hiv-1 Spreadmentioning

confidence: 99%

Adding new dimensions: towards an integrative understanding of HIV-1 spread

et al. 2014

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In vitro studies in primary or immortalized cells continue to identify essential principles governing interactions of HIV-1 with isolated target cells. Until recently, significant technical barriers prevented this wealth of information to be efficiently translated to the more complex scenario of HIV-1 spread inside the host. Our current understanding of the impact of physiological parameters on HIV-1 spread thus remains very limited. In this Review, we discuss the recent development of imaging approaches for the visualization of HIV-1 spread and their adaptation to organotypic ex vivo as well as animal models. We will focus on new concepts such as mechanisms and in vivo relevance of cell-cell transmission for HIV-1 spread and the pathobiological principles of the HIV pathogenesis factor Nef that emerge from the application of such integrative approaches using complex cell systems.

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Antibody and Antiretroviral Preexposure Prophylaxis Prevent Cervicovaginal HIV-1 Infection in a Transgenic Mouse Model

Cited by 24 publications

References 85 publications

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice

Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice

Structural Insights on the Role of Antibodies in HIV-1 Vaccine and Therapy

Adding new dimensions: towards an integrative understanding of HIV-1 spread

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