ArticlePloS one2012
Generation and characterization of a defective HIV-1 Virus as an immunogen for a therapeutic vaccine.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Potent Induction of Envelope-Specific Antibody Responses by Virus-Like Particle Immunogens Based on HIV-1 Envelopes from Patients with Early Broadly Neutralizing Responses.Journal of virology · 2022Article
- How promising are HIV-1-based virus-like particles for medical applications.Frontiers in cellular and infection microbiology · 2022Review
- Insights Into Persistent HIV-1 Infection and Functional Cure: Novel Capabilities and Strategies.Frontiers in microbiology · 2022Review
- FRET-Based Detection and Quantification of HIV-1 Virion Maturation.Frontiers in microbiology · 2021Article
- HIV-1-based Virus-like Particles that Morphologically Resemble Mature, Infectious HIV-1 Virions.Viruses · 2019Article
- Article
- HIV-1 replicates in human osteoclasts and enhances their differentiation in vitro.Retrovirology · 2015Article
- Transcription elongation regulator 1 (TCERG1) regulates competent RNA polymerase II-mediated elongation of HIV-1 transcription and facilitates efficient viral replication.Retrovirology · 2013Article
- Use of RT-defective HIV virions: new tool to evaluate specific response in chronic asymptomatic HIV-infected individuals.PloS one · 2013Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe generation of new immunogens able to elicit strong specific immune responses remains a major challenge in the attempts to obtain a prophylactic or therapeutic vaccine against HIV/AIDS. We designed and constructed a defective recombinant virus based on the HIV-1 genome generating infective but non-replicative virions able to elicit broad and strong cellular immune responses in HIV-1 seropositive individuals.
resultsViral particles were generated through transient transfection in producer cells (293-T) of a full length HIV-1 DNA carrying a deletion of 892 base pairs (bp) in the pol gene encompassing the sequence that codes for the reverse transcriptase (NL4-3/ΔRT clone). The viral particles generated were able to enter target cells, but due to the absence of reverse transcriptase no replication was detected. The immunogenic capacity of these particles was assessed by ELISPOT to determine γ-interferon production in a cohort of 69 chronic asymptomatic HIV-1 seropositive individuals. Surprisingly, defective particles produced from NL4-3/ΔRT triggered stronger cellular responses than wild-type HIV-1 viruses inactivated with Aldrithiol-2 (AT-2) and in a larger proportion of individuals (55% versus 23% seropositive individuals tested). Electron microscopy showed that NL4-3/ΔRT virions display immature morphology. Interestingly, wild-type viruses treated with Amprenavir (APV) to induce defective core maturation also induced stronger responses than the same viral particles generated in the absence of protease inhibitors.
conclusionsWe propose that immature HIV-1 virions generated from NL4-3/ΔRT viral clones may represent new prototypes of immunogens with a safer profile and stronger capacity to induce cellular immune responses than wild-type inactivated viral particles.
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Registered trials
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