Delving into the Latest Updates on Tuberculosis vaccine H56IC(Statens Serum Institute) with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

Adjuvanted TB subunit vaccine H56IC, H56/IC31 vaccine, Tuberculosis vaccine H56IC

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Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

TuberculosisPulmonary Tuberculosis

Inactive Indication

Latent TuberculosisTuberculosis, Multidrug-Resistant

Originator Organization

Statens Serum Institute

Active Organization

Statens Serum Institute

Aeras Technologies LLC

European & Developing Countries Clinical Trials Partnership

+ [1]

Inactive Organization

Aj Vaccines A/S

Oslo universitetssykehus HF

Aeras Global TB Vaccine Foundation

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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This is a phase 2, double-blind, randomized (1:1), placebo-controlled trial with two parallel groups.
H56:IC31 (investigational vaccine)
Placebo
900 HIV-negative adults with a diagnosis of drug susceptible pulmonary TB are planned to be included, recruited from TB clinics with established relationships to the trial sites at the start of their TB treatment.
5 study sites in South Africa: 2 sites from the AURUM institute (Klerksdorp and Tembisa) and 3 in Cape Town at TASK Applied Science (TASK), the University of Cape Town Lung Institute (UCTLI) and South African Tuberculosis Vaccine Initiative (SATVI) under UCT, respectively.
1 study site in Tanzania (TZ): 1 site at Mbeya Medical Research Centre (MMRC) under the National Institute for Medical Research (NIMR).

Start Date31 Jan 2019

Sponsor / Collaborator

International AIDS Vaccine Initiative, Inc.

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NCT03265977 / WithdrawnPhase 2IIT

A Randomized, Placebo Controlled, Double-Blind Phase II Study to Evaluate Safety, Immunogenicity, and Prevention of Infection With Mycobacterium Tuberculosis (Mtb) of H56:IC31 in Healthy Adolescents

This clinical trial will evaluate safety, immunogenicity, and efficacy (prevention of Mtb infection as measured by IGRA conversions) of H56:IC31 in remotely BCG vaccinated adolescents.

Start Date01 Jun 2018

Sponsor / Collaborator

Aeras Global TB Vaccine Foundation

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100 Clinical Results associated with Tuberculosis vaccine H56IC(Statens Serum Institute)

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100 Translational Medicine associated with Tuberculosis vaccine H56IC(Statens Serum Institute)

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100 Patents (Medical) associated with Tuberculosis vaccine H56IC(Statens Serum Institute)

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27

Literatures (Medical) associated with Tuberculosis vaccine H56IC(Statens Serum Institute)

01 Jun 2020·Seminars in ImmunopathologyQ2 · MEDICINE

Towards new TB vaccines

Q2 · MEDICINE

Review

Author: McShane, Helen ; Brazier, Benedict

AbstractMycobacterium tuberculosisremains the leading cause of death attributed to a single infectious organism. Bacillus Calmette-Guerin (BCG), the standard vaccine againstM. tuberculosis, is thought to prevent only 5% of all vaccine-preventable deaths due to tuberculosis, thus an alternative vaccine is required. One of the principal barriers to vaccine development againstM. tuberculosisis the complexity of the immune response to infection, with uncertainty as to what constitutes an immunological correlate of protection. In this paper, we seek to give an overview of the immunology ofM. tuberculosisinfection, and by doing so, investigate possible targets of vaccine development. This encompasses the innate, adaptive, mucosal and humoral immune systems. Though MVA85A did not improve protection compared with BCG alone in a large-scale clinical trial, the correlates of protection this has revealed, in addition to promising results from candidate such as VPM1002, M72/ASO1E and H56:IC31 point to a brighter future in the field of TB vaccine development.

01 Apr 2020·Medical Microbiology and ImmunologyQ4 · MEDICINE

Toll like-receptor agonist Pam3Cys modulates the immunogenicity of liposomes containing the tuberculosis vaccine candidate H56

Q4 · MEDICINE

Article

Author: Stenger, Steffen ; Kennerknecht, Kathrin ; Wehrstedt, Stephanie ; Pedersen, Gabriel Kristian ; Noschka, Reiner ; Grieshober, Mark ; Löffler, Florian ; Mayer, Daniel ; Christensen, Dennis

AbstractA major roadblock in the development of novel vaccines is the formulation and delivery of the antigen. Liposomes composed of a dimethyldioctadecylammonium (DDA) backbone and the adjuvant trehalose-6-6-dibehenate (TDB, termed “cationic adjuvant formulation (CAF01)”, promote immunogenicity and protective efficacy of vaccines, most notably against infection with Mycobacterium tuberculosis. Specifically, the multicomponent antigen H56 delivered by CAF01 protects against tuberculosis in mice. Here we investigated whether the inclusion of immune-modulatory adjuvants into CAF01 modulates the immunogenicity of H56/CAF01 in vitro and in vivo. Based on our recent findings we selected the active sequence of the mycobacterial 19 kDa lipoprotein, Pam3Cys, which interacts with Toll like receptor 2 to induce an antimicrobial pathway. H56/CAF01-Pam3Cys liposomes were characterized for Pam3Cys incorporation, size, toxicity and activation of primary human macrophages. Macrophages efficiently take up H56/CAF01-Pam3Cys and trigger the release of significantly higher levels of TNF, IL-12 and IL-10 than H56/CAF01 alone. To evaluate the immunogenicity in vivo, we immunized mice with H56/CAF01-Pam3Cys and measured the release of IFN-γ and IL-17A by lymph node cells and spleen cells. While the antigen-specific production of IFN-γ was reduced by inclusion of Pam3Cys into H56/CAF01, the levels of IL-17A remained unchanged. In agreement with this finding, the concentration of the IFN-γ-associated IgG2a antibodies in the serum was lower than in H56/CAF01 immunized animals. These results provide proof of concept that Toll like-receptor agonist can be included into liposomes to modulate immune responses. The discordant results between the in vitro studies with human macrophages and in vivo studies in mice highlight the relevance and complexity of comparing immune responses in different species

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 ; Ginsberg, Ann ; Ruhwald, Morten ; 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.

100 Deals associated with Tuberculosis vaccine H56IC(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	TZ	Statens Serum Institute	01 Jun 2018
Pulmonary Tuberculosis	Phase 2	-	Aeras Technologies LLC	-
Tuberculosis	Phase 1	ZA	Statens Serum Institute	01 Jun 2018
Tuberculosis	Phase 1	TZ	Statens Serum Institute	01 Jun 2018
Tuberculosis, Multidrug-Resistant	Phase 1	NO	Oslo universitetssykehus HF	01 Nov 2015
Latent Tuberculosis	Phase 1	ZA	Aeras Global TB Vaccine Foundation	01 Aug 2013
Latent Tuberculosis	Phase 1	ZA	Statens Serum Institute	01 Aug 2013
Tuberculosis	Discovery	ZA	Statens Serum Institute	01 Jun 2018

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02375698 (C-037-456, CTgov)	Phase 1	Pulmonary Tuberculosis	22	Placebo (Placebo)	gxqpkmqqou(nrqjeenlpz) = igaprgnarp ykmupptafy (aawyuimktn, gwfpjqaaxb - yxeernxfby) View more	-	18 Nov 2019
				H56:IC31 (Gr 1 H56:IC31 5/500)	fglchopgbm(hnwvjxduac) = qdwibstviv hjqetmmnau (xtfujdlsew, lfmhjhwgsv - kmcadnrzwz) View more
NCT02378207 (CTgov)	Phase 1	Tuberculosis	84	H4:IC31 (Group 1 H4:IC31)	ngycbhpbst(konyrqwuop) = doslgyihwx tcujelxxds (zgduahiogm, omuzioedhg - yfnjhldvan) View more	-	18 Nov 2019
				H56:IC31 (Group 2 H56:IC31)	ngycbhpbst(konyrqwuop) = diitazdqbr tcujelxxds (zgduahiogm, grdjqhauaj - genmiajssr) View more
NCT01967134 (CTgov)	Phase 1	Latent Tuberculosis	25	H56:IC31 (H56:IC31 (50 ug H56) LTBI Neg)	rcckkdishj(nangdafmgc) = cdcdcftubb lmtsrufwzi (htolmblove, ntnaysicop - eakmcwebea) View more	-	21 Aug 2019
				H56:IC31 (H56:IC31 (15 ug H56) LTBI Pos)	rcckkdishj(nangdafmgc) = vztfxbnkzm lmtsrufwzi (htolmblove, oodbwcoywo - gfqudfwzut) View more