ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Aerosol vaccination with AERAS-402 elicits robust cellular immune responses in the lungs of rhesus macaques but fails to protect against high-dose Mycobacterium tuberculosis challenge.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.
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Who cites it
61 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development.Frontiers in immunology · 2022Pooled it
- CD4+ T cell cytokine responses to the DAR-901 booster vaccine in BCG-primed adults: A randomized, placebo-controlled trial.PloS one · 2019Trial
- Human CD4+ T cells recognize Mycobacterium tuberculosis-infected macrophages amid broader responses.The Journal of experimental medicine · 2025Article
- Increased vaccine efficacy against tuberculosis with a recombinant BCG overexpressing the STING agonist cyclic di-AMP.bioRxiv : the preprint server for biology · 2025Article
- Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates.Nature immunology · 2024Article
- TB-vaccines: Current status & challenges.The Indian journal of medical research · 2024Review
- Evolving Horizons: Adenovirus Vectors' Timeless Influence on Cancer, Gene Therapy and Vaccines.Viruses · 2023Review
- Intravenous BCG Vaccination of Diversity Outbred Mice Results in Moderately Enhanced Protection against Challenge with Mycobacterium tuberculosis Compared to Intradermal Vaccination.Infection and immunity · 2023Article
- Spore-FP1 tuberculosis mucosal vaccine candidate is highly protective in guinea pigs but fails to improve on BCG-conferred protection in non-human primates.Frontiers in immunology · 2023Article
- Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines.Frontiers in immunology · 2023Review
- Intranasal bovine β-defensin-5 enhances antituberculosis immunity in a mouse model by a novel protein-based respiratory mucosal vaccine.Virulence · 2022Article
- Peripheral Blood Markers Correlate with the Progression of Active Tuberculosis Relative to Latent Control ofPathogens (Basel, Switzerland) · 2022Article
- Human mucosal tissue-resident memory T cells in health and disease.Mucosal immunology · 2022Review
- Therapeutic Vaccines for Tuberculosis: An Overview.Frontiers in immunology · 2022Review
- System-wide identification of myeloid markers of TB disease and HIV-induced reactivation in the macaque model of Mtb infection and Mtb/SIV co-infection.Frontiers in immunology · 2022Article
- An Update on Tuberculosis Vaccines.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Insights into the molecular determinants involved inVirulence · 2021Review
- COVID-19 cynomolgus macaque model reflecting human COVID-19 pathological conditions.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The safety and efficacy of BCG encapsulated alginate particle (BEAP) against M.tb H37Rv infection in Macaca mulatta : A pilot study.Scientific reports · 2021Article
- Protective efficacy of an attenuated Mtb ΔLprG vaccine in mice.PLoS pathogens · 2020Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Development of a vaccine against pulmonary tuberculosis may require immunization strategies that induce a high frequency of Ag-specific CD4 and CD8 T cells in the lung. The nonhuman primate model is essential for testing such approaches because it has predictive value for how vaccines elicit responses in humans. In this study, we used an aerosol vaccination strategy to administer AERAS-402, a replication-defective recombinant adenovirus (rAd) type 35 expressing Mycobacterium tuberculosis Ags Ag85A, Ag85B, and TB10.4, in bacillus Calmette-Guérin (BCG)-primed or unprimed rhesus macaques. Immunization with BCG generated low purified protein derivative-specific CD4 T cell responses in blood and bronchoalveolar lavage. In contrast, aerosolized AERAS-402 alone or following BCG induced potent and stable Ag85A/b-specific CD4 and CD8 effector T cells in bronchoalveolar lavage that largely produced IFN-γ, as well as TNF and IL-2. Such responses induced by BCG, AERAS-402, or both failed to confer overall protection following challenge with 275 CFUs M. tuberculosis Erdman, although vaccine-induced responses associated with reduced pathology were observed in some animals. Anamnestic T cell responses to Ag85A/b were not detected in blood of immunized animals after challenge. Overall, our data suggest that a high M. tuberculosis challenge dose may be a critical factor in limiting vaccine efficacy in this model. However, the ability of aerosol rAd immunization to generate potent cellular immunity in the lung suggests that using different or more immunogens, alternative rAd serotypes with enhanced immunogenicity, and a physiological challenge dose may achieve protection against M. tuberculosis.
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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.