ArticlePLoS pathogens2012
MiniCD4 microbicide prevents HIV infection of human mucosal explants and vaginal transmission of SHIV(162P3) in cynomolgus macaques.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 35 citations in OpenAlex.
- Pharmacokinetic/pharmacodynamic investigation of raltegravir with or without lamivudine in the context of HIV-1 pre-exposure prophylaxis (PrEP).The Journal of antimicrobial chemotherapy · 2021Trial
- The Role of Peptides in Combatting HIV Infection: Applications and Insights.Molecules (Basel, Switzerland) · 2024Review
- Development of Protein- and Peptide-Based HIV Entry Inhibitors Targeting gp120 or gp41.Viruses · 2019Review
- Increased, Durable B-Cell and ADCC Responses Associated with T-Helper Cell Responses to HIV-1 Envelope in Macaques Vaccinated with gp140 Occluded at the CD4 Receptor Binding Site.Journal of virology · 2017Article
- M48U1 and Tenofovir combination synergistically inhibits HIV infection in activated PBMCs and human cervicovaginal histocultures.Scientific reports · 2017Article
- Driving HIV-1 into a Vulnerable Corner by Taking Advantage of Viral Adaptation and Evolution.Frontiers in microbiology · 2017Review
- CD4-mimetic sulfopeptide conjugates display sub-nanomolar anti-HIV-1 activity and protect macaques against a SHIV162P3 vaginal challenge.Scientific reports · 2016Article
- Superior Efficacy of a Human Immunodeficiency Virus Vaccine Combined with Antiretroviral Prevention in Simian-Human Immunodeficiency Virus-Challenged Nonhuman Primates.Journal of virology · 2016Article
- Parsimonious Determination of the Optimal Infectious Dose of a Pathogen for Nonhuman Primate Models.PLoS pathogens · 2015Article
- HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth.Expert opinion on therapeutic targets · 2015Review
- Thermosensitive and mucoadhesive pluronic-hydroxypropylmethylcellulose hydrogel containing the mini-CD4 M48U1 is a promising efficient barrier against HIV diffusion through macaque cervicovaginal mucus.Antimicrobial agents and chemotherapy · 2015Article
- Prolonged expression of an anti-HIV-1 gp120 minibody to the female rhesus macaque lower genital tract by AAV gene transfer.Gene therapy · 2014Article
- Adding new dimensions: towards an integrative understanding of HIV-1 spread.Nature reviews. Microbiology · 2014Review
- Protective effect of vaginal application of neutralizing and nonneutralizing inhibitory antibodies against vaginal SHIV challenge in macaques.Mucosal immunology · 2014Article
- Which Antibody Functions are Important for an HIV Vaccine?Frontiers in immunology · 2014Review
- Antibody-based concepts for multipurpose prevention technologies.Antiviral research · 2013Review
- Animal models for microbicide safety and efficacy testing.Current opinion in HIV and AIDS · 2013Review
- Interfacial cavity filling to optimize CD4-mimetic miniprotein interactions with HIV-1 surface glycoprotein.Journal of medicinal chemistry · 2013Article
- Structural basis for highly effective HIV-1 neutralization by CD4-mimetic miniproteins revealed by 1.5 Å cocrystal structure of gp120 and M48U1.Structure (London, England : 1993) · 2013Article
- Blocking HIV-1 gp120 at the Phe43 cavity: if the extension fits….Structure (London, England : 1993) · 2013Article
Corrections and comments
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Authors and funding
15 authors at 11 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In complement to an effective vaccine, development of potent anti-HIV microbicides remains an important priority. We have previously shown that the miniCD4 M48U1, a functional mimetic of sCD4 presented on a 27 amino-acid stable scaffold, inhibits a broad range of HIV-1 isolates at sub-nanomolar concentrations in cellular models. Here, we report that M48U1 inhibits efficiently HIV-1(Ba-L) in human mucosal explants of cervical and colorectal tissues. In vivo efficacy of M48U1 was evaluated in nonhuman primate (NHP) model of mucosal challenge with SHIV(162P3) after assessing pharmacokinetics and pharmacodynamics of a miniCD4 gel formulation in sexually matured female cynomolgus macaques. Among 12 females, half were treated with hydroxyethylcellulose-based gel (control), the other half received the same gel containing 3 mg/g of M48U1, one hour before vaginal route challenge with 10 AID(50) of SHIV(162P3). All control animals were infected with a peak plasma viral load of 10(5)-10(6) viral RNA (vRNA) copies per mL. In animals treated with miniCD4, 5 out of 6 were fully protected from acquisition of infection, as assessed by qRT-PCR for vRNA detection in plasma, qPCR for viral DNA detection in PBMC and lymph node cells. The only infected animal in this group had a delayed peak of viremia of one week. These results demonstrate that M48U1 miniCD4 acts in vivo as a potent entry inhibitor, which may be considered in microbicide developments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.