Trial reportEBioMedicine2016
Safety and Immunogenicity of the Recombinant BCG Vaccine AERAS-422 in Healthy BCG-naïve Adults: A Randomized, Active-controlled, First-in-human Phase 1 Trial.
Trial report in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01340820 (A Phase 1, Randomized, Controlled, Double-blind, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of AERAS-422 in Healthy Adults), which is not on this map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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.
A Phase 1, Randomized, Controlled, Double-blind, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of AERAS-422 in Healthy Adults
Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Development and application of the direct mycobacterial growth inhibition assay: a systematic review.Frontiers in immunology · 2024Pooled it
- Safety and immunogenicity of a thermostable ID93 + GLA-SE tuberculosis vaccine candidate in healthy adults.Nature communications · 2023Trial
- Adjunctive use of celecoxib with anti-tuberculosis drugs: evaluation in a whole-blood bactericidal activity model.Scientific reports · 2018Trial
- Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.PLoS pathogens · 2017Trial
- Antigen 85B ofVaccines · 2026Review
- Immunotherapy for tuberculosis: emerging modalities, cross-disciplinary innovations, and roadmaps for drug-resistant disease.Frontiers in immunology · 2026Review
- scKAN: interpretable single-cell analysis for cell-type-specific gene discovery and drug repurposing via Kolmogorov-Arnold networks.Genome biology · 2025Article
- BCG therapy in bladder cancer and its tumor microenvironment interactions.Clinical microbiology reviews · 2025Review
- Chronic inflammation degrades CD4 T cell immunity to prior vaccines in treated HIV infection.Nature communications · 2024Article
- Phase 1 Open-Label Dose Escalation Trial for the Development of a Human Bacillus Calmette-Guérin Challenge Model for Assessment of Tuberculosis Immunity In Vivo.The Journal of infectious diseases · 2024Article
- The Use of Particulate Systems for Tuberculosis Prophylaxis and Treatment: Opportunities and Challenges.Microorganisms · 2023Review
- Bridging the gaps to overcome major hurdles in the development of next-generation tuberculosis vaccines.Frontiers in immunology · 2023Review
- Role of MHC class I pathways inFrontiers in cellular and infection microbiology · 2023Review
- Editorial: Research advances of tuberculosis vaccine and its implication on COVID-19.Frontiers in immunology · 2023Article
- Fighting Tuberculosis: In Search of a BCG Replacement.Microorganisms · 2022Review
- Recent Developments in Mycobacteria-Based Live Attenuated Vaccine Candidates for Tuberculosis.Biomedicines · 2022Review
- Evaluating the Performance of PPE44, HSPX, ESAT-6 and CFP-10 Factors in Tuberculosis Subunit Vaccines.Current microbiology · 2022Review
- Recombinant BCG to Enhance Its Immunomodulatory Activities.Vaccines · 2022Review
- An Update on Tuberculosis Vaccines.Methods in molecular biology (Clifton, N.J.) · 2022Article
- A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundWe report a first-in-human trial evaluating safety and immunogenicity of a recombinant BCG, AERAS-422, over-expressing TB antigens Ag85A, Ag85B, and Rv3407 and expressing mutant perfringolysin.
methodsThis was a randomized, double-blind, dose-escalation trial in HIV-negative, healthy adult, BCG-naïve volunteers, negative for prior exposure to Mtb, at one US clinical site. Volunteers were randomized 2:1 at each dose level to receive a single intradermal dose of AERAS-422 (>10(5)-<10(6)CFU=low dose, ≥10(6)-<10(7)CFU=high dose) or non-recombinant Tice BCG (1-8×10(5)CFU). Randomization used an independently prepared randomly generated sequence of treatment assignments. The primary and secondary outcomes were safety and immunogenicity, respectively, assessed in all participants through 182days post-vaccination. ClinicalTrials.gov registration number: NCT01340820.
findingsBetween Nov 2010 and Aug 2011, 24 volunteers were enrolled (AERAS-422 high dose, n=8; AERAS-422 low dose, n=8; Tice BCG, n=8); all were included in the safety and immunogenicity analyses. All 24 subjects had at least one adverse event, primarily expected local reactions. High dose AERAS-422 vaccination induced Ag85A- and Ag85B-specific lymphoproliferative responses and marked anti-mycobacterial activity in a whole blood bactericidal activity culture assay (WBA), but was associated with varicella zoster virus (VZV) reactivation in two vaccinees. These volunteers displayed high BCG-specific IFN-γ responses pre- and post-vaccination possibly predisposing them to autocrine/paracrine negative regulation of immune control of latent VZV. A systems biology transcriptomal approach identified positive correlations between post-vaccination T cell expression modules and WBA, and negative correlations between post-vaccination monocyte expression modules and WBA. The expression of one key macrophage marker (F4/80) was constitutively elevated in the two volunteers with zoster.
interpretationThe unexpected development of VZV in two of eight healthy adult vaccine recipients resulted in discontinuation of AERAS-422 vaccine development. Immunological and transcriptomal data identified correlations with the development of TB immunity and VZV that require further investigation.
fundingAeras, FDA, Bill and Melinda Gates Foundation.
Indexed as
Identifiers
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.