AERAS-404 / Sanofi - LARVOL DELTA

Adolescent BCG revaccination induces a phenotypic shift in CD4+ T cell responses to Mycobacterium tuberculosis. (PubMed, Nat Commun) - "In a companion phase 1b trial, HVTN 602/Aeras A-042, we characterize in-depth the cellular responses to BCG revaccination or to a H4:IC31 vaccine boost to identify T cell subsets that could be responsible for the protection observed...Additionally, a small cluster of Th17 TEM cells induced by BCG revaccination expresses high levels of CD103; these may represent recirculating tissue-resident memory cells that could provide pulmonary immune protection. Together, these results identify unique populations of CD4+ T cells with potential to be immune correlates of protection conferred by BCG revaccination."

Journal • P1 data • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis • CD4 • ITGAE

[VIRTUAL] Phase 2b controlled trial of M72/AS01E Vaccine to prevent Tuberculosis and Prevention of M. tuberculosis infection with H4:IC31 Vaccine or BCG Revaccination. (NAPCON 2020) - No abstract available

P2b data • Infectious Disease • Respiratory Diseases • Tuberculosis

Vaccine strategies for the Mtb/HIV copandemic. (PubMed, NPJ Vaccines) - "Recent advances in the TB vaccines led to the development of promising candidates such as MTBVAC, the BCG revaccination approach, H4:IC31, H56:IC31, M72/AS01 and more recently, intravenous (IV) BCG. Modification of these vaccine candidates against TB/HIV coinfection could reveal key correlates of protection in a representative animal model. This review discusses the (i) potential TB vaccine candidates that can be exploited for use as a dual vaccine against TB/HIV copandemic (ii) progress made in the realm of TB/HIV dual vaccine candidates in small animal model, NHP model, and human clinical trials (iii) the failures and promising targets for a successful vaccine strategy while delineating the correlates of vaccine-induced protection."

Journal • Review • Human Immunodeficiency Virus • Immunology • Infectious Disease • Tuberculosis

Multidimensional analyses reveal modulation of adaptive and innate immune subsets by tuberculosis vaccines. (PubMed, Commun Biol) - "Responses are measured by whole blood intracellular cytokine staining at baseline and 70 days after vaccination with H4:IC31 (subunit vaccine containing Ag85B and TB10.4), Bacille Calmette-Guerin (BCG, a live attenuated vaccine) or placebo (n = ~30 per group)...In vitro BCG re-stimulation also triggers responses by donor-unrestricted T cells, which may contribute to host responses against mycobacteria. BCG, which demonstrated efficacy against sustained Mycobacterium tuberculosis infection, modulates multiple immune cell subsets, in particular conventional Th1 and Th22 cells, which should be investigated in discovery studies of correlates of protection."

Journal • Infectious Disease • Tuberculosis • IFNG • IL2

An in vitro functional assay to measure the biological activity of TB vaccine candidate H4-IC31. (PubMed, Vaccine) - "The CSA is specific to the H4-IC31 vaccine, determines the RSA of H4-IC31 in the range of 50% to 150% of the reference standard, and is stability indicating as it detects differences in RSA between intact and heat treated H4-IC31. Although the CSA does not provide a link to clinical efficacy, it fulfills the critical requirements for a biological potency test to assess TB vaccine candidates and can be used along with biochemical and immunochemical assays to define a product profile during clinical development, while eliminating the use of animals for product testing."

Journal • Preclinical • Infectious Disease • Tuberculosis

Designing tuberculosis vaccine efficacy trials - lessons from recent studies. (PubMed, Expert Rev Vaccines) - "They are the first Prevention of Infection trial, evaluating the H4:IC31 candidate or BCG revaccination in high-risk adolescents and a Prevention of Disease trial evaluating the M72/AS01 candidate in M.tuberculosis-infected, healthy adults...Expert opinion: The opportunities created by these two trials for gaining critically important knowledge are game-changing for TB vaccine development. Their results clearly establish feasibility in the relatively near term of developing novel, effective vaccines that could be crucial to ending the TB epidemic."

Clinical • Journal • Infectious Disease • Tuberculosis

A-042: Phase 1b Safety and Immunogenicity Trial of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescents (clinicaltrials.gov) - P1b; N=84; Active, not recruiting; Sponsor: Aeras; Phase classification: P1 ➔ P1b; Trial primary completion date: May 2016 ➔ Nov 2016

Phase classification • Trial primary completion date • Biosimilar • Gene Therapies • Immunology

Phase 1b Safety and Immunogenicity Trial of BCG Revaccination, H4:IC31, and H56:IC31 in Healthy, HIV-1-Uninfected Adolescents (clinicaltrials.gov) - P1; N=84; Recruiting; Sponsor: Aeras; Not yet recruiting -> Recruiting

Enrollment open • Biosimilar • Immunology

C-015-404: Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in BCG-Primed Infants (clinicaltrials.gov) - P1/2; N=243; Completed; Sponsor: Aeras; Active, not recruiting ➔ Completed

Trial completion • Biosimilar • Human Immunodeficiency Virus • Infectious Disease • Tuberculosis

A phase 1b randomized study of the safety and immunological responses to vaccination with H4:IC31, H56:IC31, and BCG revaccination in Mycobacterium tuberculosis-uninfected adolescents in Cape Town, South Africa. (PubMed, EClinicalMedicine) - P1b | "Characterization of the assays and the immunogenicity of these vaccines may help to identify valuable markers of protection for upcoming immune correlates analyses of C-040-404 and future TB vaccine efficacy trials. NIAID and Aeras."

Clinical • Journal • P1 data