ArticlePloS one2014
Immune-correlates analysis of an HIV-1 vaccine efficacy trial reveals an association of nonspecific interferon-γ secretion with increased HIV-1 infection risk: a cohort-based modeling study.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 24 citations in OpenAlex.
- Review
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- Dynamic immune markers predict HIV acquisition and augment associations with sociobehavioral factors for HIV exposure.iScience · 2022Article
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- Mycobacterium tuberculosis infection, immune activation, and risk of HIV acquisition.PloS one · 2022Article
- Vaccine-associated enhanced disease in humans and animal models: Lessons and challenges for vaccine development.Frontiers in microbiology · 2022Review
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- Understanding Post Entry Sorting of Adenovirus Capsids; A Chance to Change Vaccine Vector Properties.Viruses · 2021Review
- Engineered Antigen-Specific T Cells Secreting Broadly Neutralizing Antibodies: Combining Innate and Adaptive Immune Response against HIV.Molecular therapy. Methods & clinical development · 2020Article
- Long-term mucosal T cell activation and homing phenotypes in recipients of an Ad5-vectored HIV vaccine.Vaccine · 2020Article
- Article
- Lessons Learned in Developing a Commercial FIV Vaccine: The Immunity Required for an Effective HIV-1 Vaccine.Viruses · 2018Review
- Preventing HIV infection without targeting the virus: how reducing HIV target cells at the genital tract is a new approach to HIV prevention.AIDS research and therapy · 2017Review
- Conserved HIV Epitopes for an Effective HIV Vaccine.Journal of clinical & cellular immunology · 2017Article
- Trained Immunity and Susceptibility to HIV.Clinical and vaccine immunology : CVI · 2017Article
- Balancing Trained Immunity with Persistent Immune Activation and the Risk of Simian Immunodeficiency Virus Infection in Infant Macaques Vaccinated with Attenuated Mycobacterium tuberculosis or Mycobacterium bovis BCG Vaccine.Clinical and vaccine immunology : CVI · 2017Article
- HIV Susceptibility of human antigen-specific CD4 T cells in AIDS pathogenesis and vaccine response.Expert review of vaccines · 2016Review
- New prospects for a preventive HIV-1 vaccine.Journal of virus eradication · 2015Article
- Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundElevated risk of HIV-1 infection among recipients of an adenovirus serotype 5 (Ad5)-vectored HIV-1 vaccine was previously reported in the Step HIV-1 vaccine efficacy trial. We assessed pre-infection cellular immune responses measured at 4 weeks after the second vaccination to determine their roles in HIV-1 infection susceptibility among Step study male participants.
methodsWe examined ex vivo interferon-γ (IFN-γ) secretion from peripheral blood mononuclear cells (PBMC) using an ELISpot assay in 112 HIV-infected and 962 uninfected participants. In addition, we performed flow cytometric assays to examine T-cell activation, and ex vivo IFN-γ and interleukin-2 secretion from CD4(+) and CD8(+) T cells. We accounted for the sub-sampling design in Cox proportional hazards models to estimate hazard ratios (HRs) of HIV-1 infection per 1-log(e) increase of the immune responses.
findingsWe found that HIV-specific immune responses were not associated with risk of HIV-1 infection. However, each 1-log(e) increase of mock responses measured by the ELISpot assay (i.e., IFN-γ secretion in the absence of antigen-specific stimulation) was associated with a 62% increase of HIV-1 infection risk among vaccine recipients (HR = 1.62, 95% CI: (1.28, 2.04), p<0.001). This association remains after accounting for CD4(+) or CD8(+) T-cell activation. We observed a moderate correlation between ELISpot mock responses and CD4(+) T-cells secreting IFN-γ (ρ = 0.33, p = 0.007). In addition, the effect of the Step vaccine on infection risk appeared to vary with ELISpot mock response levels, especially among participants who had pre-existing anti-Ad5 antibodies (interaction p = 0.04).
conclusionsThe proportion of cells, likely CD4(+) T-cells, producing IFN-γ without stimulation by exogenous antigen appears to carry information beyond T-cell activation and baseline characteristics that predict risk of HIV-1 infection. These results motivate additional investigation to understand the potential link between IFN-γ secretion and underlying causes of elevated HIV-1 infection risk among vaccine recipients in the Step study.
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