ArticleProceedings of the National Academy of Sciences of the United States of America2014
Preferential infection of human Ad5-specific CD4 T cells by HIV in Ad5 naturally exposed and recombinant Ad5-HIV vaccinated individuals.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 48 citations in OpenAlex.
- Live attenuated varicella-zoster virus vaccine does not induce HIV target cell activation.The Journal of clinical investigation · 2019Trial
- Higher T-Cell Responses Induced by DNA/rAd5 HIV-1 Preventive Vaccine Are Associated With Lower HIV-1 Infection Risk in an Efficacy Trial.The Journal of infectious diseases · 2017Trial
- Preferential engagement of the anti-inflammatory ATP/adenosine axis by HIV vaccine candidate with V1-deleted envelope in male rhesus macaques.Cell reports. Medicine · 2026Article
- Immunotherapy-induced cytotoxic T follicular helper cells reduce numbers of retrovirus-infected reservoir cells in B cell follicles.PLoS pathogens · 2023Article
- The use of adenoviral vectors in gene therapy and vaccine approaches.Genetics and molecular biology · 2022Article
- Immunogenicity of an inactivated SARS-CoV-2 vaccine in people living with HIV-1: a non-randomized cohort study.EClinicalMedicine · 2022Article
- Current approaches to HIV vaccine development: a narrative review.Journal of the International AIDS Society · 2021Review
- A Zigzag but Upward Way to Develop an HIV-1 Vaccine.Vaccines · 2020Review
- Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine.Vaccine · 2020Article
- T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers.Nature medicine · 2020Article
- Epigenetic Suppression of HIV in Myeloid Cells by the BRD4-Selective Small Molecule Modulator ZL0580.Journal of virology · 2020Article
- Review
- Modulation of the CCR5 Receptor/Ligand Axis by Seminal Plasma and the Utility ofJournal of virology · 2019Article
- Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers.Immunity · 2019Article
- CD4AIDS research and human retroviruses · 2018Review
- Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.PLoS pathogens · 2018Article
- Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection.PLoS pathogens · 2018Article
- Regulating Innate and Adaptive Immunity for Controlling SIV Infection by 25-Hydroxycholesterol.Frontiers in immunology · 2018Article
- Expression of Herpes Simplex Virus Thymidine Kinase/Ganciclovir by RNA Trans-Splicing Induces Selective Killing of HIV-Producing Cells.Molecular therapy. Nucleic acids · 2017Article
- Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Efficacy trials of adenovirus 5-vectored candidate HIV vaccines [recombinant Ad5 (rAd5)-HIV] were halted for futility due to lack of vaccine efficacy and unexpected excess HIV infections in the vaccine recipients. The potential immunologic basis for these observations is unclear. We comparatively evaluated the HIV susceptibility and phenotypes of human CD4 T cells specific to Ad5 and CMV, two viruses that have been used as HIV vaccine vectors. We show that Ad5-specific CD4 T cells, either induced by natural Ad5 exposure or expanded by rAd5 vaccination, are highly susceptible to HIV in vitro and are preferentially lost in HIV-infected individuals compared with CMV-specific CD4 T cells. Further investigation demonstrated that Ad5-specific CD4 T cells selectively display a proinflammatory Th17-like phenotype and express macrophage inflammatory protein 3α and α4β7 integrin, suggestive of gut mucosa homing potential of these cells. Analysis of HIV p24 and cytokine coexpression using flow cytometry revealed preferential infection of IL-17- and IL-2-producing, Ad5-specific CD4 T cells by HIV in vitro. Our data suggest a potential mechanism explaining the excess HIV infections in vaccine recipients after rAd5-HIV vaccination and highlight the importance of testing the HIV susceptibility of vaccine-generated, vector and insert-specific CD4 T cells in future HIV vaccine studies.
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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.