Delving into the Latest Updates on Tuberculosis vaccine H4IC(Statens Serum Institute) with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Adjuvanted TB subunit vaccine H4IC, H4/IC31 vaccine, Tuberculosis vaccine H4IC

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Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Pulmonary Tuberculosis

Inactive Indication-

Originator Organization

Statens Serum Institute

Active Organization

Sanofi

Statens Serum Institute

Aeras Technologies LLC

Inactive Organization

Aeras Global TB Vaccine Foundation

Sanofi Pasteur

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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The aims of the phase 1b trial described here are to facilitate identification of assays and immune responses that could then be evaluated as correlates of risk and correlates of protection in efficacy studies and ultimately to provide leads for biomarkers of protection against tuberculosis. This study will complement one ongoing study (NCT02075203) evaluating the prevention of M. Tuberculosis infection using H4:IC31 (also known as AERAS-404).

Start Date01 May 2015

Sponsor / Collaborator

Aeras Global TB Vaccine Foundation

[+3]

PACTR201512001069358 / CompletedPhase 2IIT

A Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents

Start Date18 Feb 2014

Sponsor / Collaborator

Aeras Global TB Vaccine Foundation

[+1]

NCT02075203 / CompletedPhase 2IIT

A Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents

Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection with Mycobacterium tuberculosis of AERAS-404 and BCG Revaccination in Healthy Adolescents

Start Date01 Feb 2014

Sponsor / Collaborator

Aeras Global TB Vaccine Foundation

[+1]

100 Clinical Results associated with Tuberculosis vaccine H4IC(Statens Serum Institute)

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100 Translational Medicine associated with Tuberculosis vaccine H4IC(Statens Serum Institute)

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100 Patents (Medical) associated with Tuberculosis vaccine H4IC(Statens Serum Institute)

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16

Literatures (Medical) associated with Tuberculosis vaccine H4IC(Statens Serum Institute)

01 Apr 2020·EClinicalMedicine

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

Article

Author: Andersen, Peter L ; Andersen-Nissen, Erica ; Ruhwald, Morten ; Ginsberg, Ann ; DiazGranados, Carlos A ; De Rosa, Stephen C ; Rutkowski, Kathryn T ; Seaton, Kelly E ; McElrath, M Juliana ; Dintwe, One ; Hutter, Julia ; Randhawa, April K ; Williams, Anthony ; Miner, Maurine D ; Middelkoop, Keren ; Kublin, James G ; Tait, Dereck ; Tomaras, Georgia D ; Fiore-Gartland, Andrew ; Bekker, Linda-Gail ; Kromann, Ingrid

BACKGROUNDTuberculosis (TB) remains the leading cause of infectious disease-related death. Recently, a trial of BCG revaccination and vaccination with H4:IC31, a recombinant protein vaccine, in South African adolescents (Aeras C-040-404) showed efficacy in preventing sustained QuantiFERON (QFT) conversion, a proxy for Mycobacterium tuberculosis (M.tb) infection. A phase 1b trial of 84 South African adolescents was conducted, concurrent with Aeras C-040-404, to assess the safety and immunogenicity of H4:IC31, H56:IC31 and BCG revaccination, and to identify and optimize immune assays for identification of candidate correlates of protection in efficacy trials.METHODSTwo doses of H4:IC31 and H56:IC31 vaccines were administered intramuscularly (IM) 56 days apart, and a single dose of BCG (2-8 × 10⁵ CFU) was administered intradermally (ID). T-cell and antibody responses were measured using intracellular cytokine staining and binding antibody assays, respectively. Binding antibodies and CD4+/CD8+ T-cell responses to H4- and H56-matched antigens were measured in samples from all participants. The study was designed to characterize safety and immunogenicity and was not powered for group comparisons. (Clinicaltrials.gov NCT02378207).FINDINGSIn total, 481 adolescents (mean age 13·9 years) were screened; 84 were enrolled (54% female). The vaccines were generally safe and well-tolerated, with no reported severe adverse events related to the study vaccines. H4:IC31 and H56:IC31 elicited CD4+ T cells recognizing vaccine-matched antigens and H4- and H56-specific IgG binding antibodies. The highest vaccine-induced CD4+ T-cell response rates were for those recognizing Ag85B in the H4:IC31 and H56:IC31 vaccinated groups. BCG revaccination elicited robust, polyfunctional BCG-specific CD4+ T cells, with no increase in H4- or H56-specific IgG binding antibodies. There were few antigen-specific CD8+ T-cell responses detected in any group.INTERPRETATIONBCG revaccination administered as a single dose ID and both H4:IC31 and H56:IC31 administered as 2 doses IM had acceptable safety profiles in healthy, QFT-negative, previously BCG-vaccinated adolescents. 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.FUNDINGNIAID and Aeras.

04 May 2019·Expert Review of VaccinesQ2 · MEDICINE

Designing tuberculosis vaccine efficacy trials – lessons from recent studies

Q2 · MEDICINE

Article

Author: Ginsberg, Ann M.

INTRODUCTIONTuberculosis (TB) is the leading infectious killer globally and new TB vaccines will be crucial to ending the epidemic. Since the introduction in 1921 of the only currently licensed TB vaccine, BCG, very few novel vaccine candidates or strategies have advanced into clinical efficacy trials. Areas covered: Recently, however, two TB vaccine efficacy trials with novel designs have reported positive results and are now driving new momentum in the field. 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_E candidate in M.tuberculosis-infected, healthy adults. These trials are briefly reviewed, and lessons learned are proposed to help inform the design of future efficacy trials. The references cited were chosen by the author based on PubMed searches to provide context for the opinions expressed in this Perspective article. 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.

01 May 2019·VaccineQ3 · MEDICINE

An in vitro functional assay to measure the biological activity of TB vaccine candidate H4-IC31

Q3 · MEDICINE

Article

Author: Gajewska, Beata ; Ming, Marin ; Piras, Fabienne ; Bernardo, Lidice ; Kapoor, Nidhi ; Kolattukudy, Pappachan ; Gisonni-Lex, Lucy ; Chan, Leslie G ; Williams, Kimberley ; Salha, Danielle ; Pagnon, Anke ; Su, Jin

Potency assays for vaccine products are an important regulatory requirement, and are used to assess product quality and consistency prior to lot release for clinical testing. Ideally they measure an established correlate of efficacy or protection. In cases where there is no known correlate of protection, however, a functional assay that measures a biological response to a vaccine can be applied as a potency assay. Here we describe an in vitro assay which quantitatively measures human T cell activation as a biological response to the TB vaccine candidate H4-IC31. The Cytokine Secretion Assay (CSA) is based on the ability of peripheral blood mononuclear cells (PBMCs) from a Bacillus Calmette-Guérin (BCG)-vaccinated human donor to process and respond to H4-IC31. The ability of H4-IC31 to stimulate a cellular immune response is measured through the quantification of secreted IFNγ and is reported as relative stimulatory activity (RSA) compared to an in-house reference standard. 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.

100 Deals associated with Tuberculosis vaccine H4IC(Statens Serum Institute)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Tuberculosis	Phase 2	ZA	Statens Serum Institute	01 Jul 2013
Pulmonary Tuberculosis	Phase 2	-	Sanofi	-
Pulmonary Tuberculosis	Phase 2	-	Statens Serum Institute	-
Pulmonary Tuberculosis	Phase 2	-	Aeras Technologies LLC	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02378207 (CTgov)	Phase 1	Tuberculosis	84	H4:IC31 (Group 1 H4:IC31)	eyndzrnoan(klnphbyyxk) = ppzheazaik jjjuzagpnp (pbpyqecxgi, jdirrpraca - loerzngpjd) View more	-	18 Nov 2019
				H56:IC31 (Group 2 H56:IC31)	eyndzrnoan(klnphbyyxk) = ripagutqqv jjjuzagpnp (pbpyqecxgi, ehmohrzjts - ywihikckyb) View more
NCT02075203 (C-040-404, CTgov)	Phase 2	Tuberculosis	989	AERAS-404 (AERAS-404 (15 mcgH4/500 Nmol IC31))	nkdjczthrj(hzgganntut) = qeplfsewxy ifzdnapxtt (zvmxxrsutz, pporhaenup - vrrlavubqs) View more	-	29 Jul 2019
				Bacillus Calmette-Guérin (BCG) (Bacillus Calmette-Guérin (BCG))	nkdjczthrj(hzgganntut) = wtogaonnlk ifzdnapxtt (zvmxxrsutz, aulfbpwivf - fhrvrnztuf) View more