ArticleProceedings of the National Academy of Sciences of the United States of America2009
Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
What it found
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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
92 citing papers in PubMed, 143 citations in OpenAlex.
- Trial
- Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.The Lancet. Infectious diseases · 2014Trial
- Sexual risk behaviors, circumcision status, and preexisting immunity to adenovirus type 5 among men who have sex with men participating in a randomized HIV-1 vaccine efficacy trial: step study.Journal of acquired immune deficiency syndromes (1999) · 2012Trial
- Trial
- Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine.Current opinion in HIV and AIDS · 2010Trial
- A scientific journey through viral immunology, vaccines, and neuroinflammation.Human vaccines & immunotherapeutics · 2026Article
- 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
- The immunogenicity and safety of adenoviral-based vaccines.Current opinion in allergy and clinical immunology · 2026Review
- Pre-Human Immunodeficiency Virus (HIV) infection Th17 CD4+ T cells as predictors of early HIV disease progression.PLoS pathogens · 2026Article
- ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates.NPJ vaccines · 2025Article
- MicroRNAs in HIV infection: dual regulators of viral replication and host immunity.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Pre-Human Immunodeficiency Virus (HIV) α4β7hi CD4+ T Cells and HIV Risk Among Heterosexual Individuals in Africa.The Journal of infectious diseases · 2025Article
- Exploring synergies between B- and T-cell vaccine approaches to optimize immune responses against HIV-workshop report.NPJ vaccines · 2024Article
- A first-in-human germline-targeting HIV nanoparticle vaccine induced broad and publicly targeted helper T cell responses.Science translational medicine · 2023Article
- Differential Homing Receptor Profiles of Lymphocytes Induced by Attenuated versus LiveVaccines · 2022Article
- Adenovirus-based vaccines-a platform for pandemic preparedness against emerging viral pathogens.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- The use of adenoviral vectors in gene therapy and vaccine approaches.Genetics and molecular biology · 2022Article
- Adenovirus-Extracellular Protein Interactions and Their Impact on Innate Immune Responses by Human Mononuclear Phagocytes.Viruses · 2020Review
- 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
32 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 2 countries.
Funding
Abstract
In the recently halted HIV type 1 (HIV-1) vaccine STEP trial, individuals that were seropositive for adenovirus serotype 5 (Ad5) showed increased rates of HIV-1 infection on vaccination with an Ad5 vaccine. We propose that this was due to activation and expansion of Ad5-specific mucosal-homing memory CD4 T cells. To test this hypothesis, Ad5 and Ad11 antibody titers were measured in 20 healthy volunteers. Dendritic cells (DCs) from these individuals were pulsed with replication defective Ad5 or Ad11 and co-cultured with autologous lymphocytes. Cytokine profiles, proliferative capacity, mucosal migration potential, and susceptibility to HIV infection of the adenovirus-stimulated memory CD4 T cells were measured. Stimulation of T cells from healthy Ad5-seropositive but Ad11-seronegative individuals with Ad5, or serologically distinct Ad11 vectors induced preferential expansion of adenovirus memory CD4 T cells expressing alpha(4)beta(7) integrins and CCR9, indicating a mucosal-homing phenotype. CD4 T-cell proliferation and IFN-gamma production in response to Ad stimulation correlated with Ad5 antibody titers. However, Ad5 serostatus did not correlate with total cytokine production upon challenge with Ad5 or Ad11. Expanded Ad5 and Ad11 memory CD4 T cells showed an increase in CCR5 expression and higher susceptibility to infection by R5 tropic HIV-1. This suggests that adenoviral-based vaccination against HIV-1 in individuals with preexisting immunity against Ad5 results in preferential expansion of HIV-susceptible activated CD4 T cells that home to mucosal tissues, increases the number of virus targets, and leads to a higher susceptibility to HIV acquisition.
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What OpenQuestion holds
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.