Delving into the Latest Updates on Tuberculosis vaccine(Aeras Technologies LLC) with Synapse

Overview

Basic Info

Drug Type

Recombinant vector vaccine, Prophylactic vaccine

Synonyms

Tuberculosis vaccine

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Infectious DiseasesRespiratory Diseases

Active Indication

Pulmonary TuberculosisTuberculosis

Inactive Indication-

Originator Organization

Aeras Technologies LLC

Active Organization

Crucell Holdings, Inc.

Crucell

Aeras Technologies LLC

+ [3]

Inactive Organization-

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

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This trial will investigate the administration of two new tuberculosis vaccines, called AERAS-402 and MVA85A. The purpose of this trial is to assess what happens when both of these vaccines are given one after the other. The trial will assess the safety of both vaccines and also their ability to stimulate an immune response within the body. It is hoped that when these two vaccines are given in sequence, the combined immune response is even better than when each vaccine is used individually.

Start Date01 Sep 2012

Sponsor / Collaborator

University of Oxford

[+4]

NCT01378312 / CompletedPhase 1IIT

A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-402 When Administered to HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection

This Phase I study will be conducted as a randomized, double-blind, placebo-controlled study in healthy adult subjects who are HIV-negative, BCG-vaccinated, and have no evidence of tuberculosis infection. The study will be conducted at one clinical research site in India.
The available live tuberculosis vaccine, Bacillus Calmette-Guérin (BCG), provides incomplete protection against pulmonary tuberculosis. For unknown reasons, a BCG revaccination or "booster", while not toxic, does not provide much additional protection. AERAS-402 presents tuberculosis antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. Since BCG-vaccinated individuals are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to individuals already vaccinated with BCG.

Start Date01 Feb 2011

Sponsor / Collaborator

Aeras Global TB Vaccine Foundation

100 Clinical Results associated with Tuberculosis vaccine(Aeras Technologies LLC)

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100 Translational Medicine associated with Tuberculosis vaccine(Aeras Technologies LLC)

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100 Patents (Medical) associated with Tuberculosis vaccine(Aeras Technologies LLC)

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880

Literatures (Medical) associated with Tuberculosis vaccine(Aeras Technologies LLC)

01 Dec 2024·International Journal of Pharmaceutics

Evaluation of PLGA, lipid-PLGA hybrid nanoparticles, and cationic pH-sensitive liposomes as tuberculosis vaccine delivery systems in a Mycobacterium tuberculosis challenge mouse model – A comparison

Article

Author: Geluk, Annemieke ; van Veen, Suzanne ; Limpens, Ronald W A L ; Franken, Kees L.M.C. ; van den Eeden, Susan J F ; Franken, Kees L M C ; Ottenhoff, Tom H M ; van Veen, S. ; van Meijgaarden, Krista E ; Neustrup, Malene A ; Szachniewicz, M.M. ; Szachniewicz, Mikołaj M ; Bouwstra, J.A. ; Neustrup, M.A. ; van den Eeden, S.J.F. ; Koning, R.I. ; Limpens, R.W.A.L. ; Koning, Roman I ; van Meijgaarden, K.E. ; Geluk, A. ; Bouwstra, Joke A ; Ottenhoff, T.H.M.

Tuberculosis (TB) continues to pose a global threat for millennia, currently affecting over 2 billion people and causing 10.6 million new cases and 1.3 million deaths annually. The only existing vaccine, Mycobacterium Bovis Bacillus Calmette-Guérin (BCG), provides highly variable and inadequate protection in adults and adolescents. This study explores newly developed subunit tuberculosis vaccines that use a multistage protein fusion antigen Ag85b-ESAT6-Rv2034 (AER). The protection efficacy, as well as in vivo induced immune responses, were compared for five vaccines: BCG; AER-CpG/MPLA mix; poly(D,L-lactic-co-glycolic acid) (PLGA); lipid-PLGA hybrid nanoparticles (NPs); and cationic pH-sensitive liposomes (the latter three delivering AER together with CpG and MPLA). All vaccines, except the AER-adjuvant mix, induced protection in Mycobacterium tuberculosis (Mtb)-challenged C57/Bl6 mice as indicated by a significant reduction in bacterial burden in lungs and spleens of the animals. Four AER-based vaccines significantly increased the number of circulating multifunctional CD4⁺ and CD8⁺ T-cells producing IL-2, IFNγ, and TNFα, exhibiting a central memory phenotype. Furthermore, AER-based vaccines induced an increase in CD69⁺ B-cell counts as well as high antigen-specific antibody titers. Unexpectedly, none of the observed immune responses were associated with the bacterial burden outcome, such that the mechanism responsible for the observed vaccine-induced protection of these vaccines remains unclear. These findings suggest the existence of non-classical protective mechanisms for Mtb infection, which could, once identified, provide interesting targets for novel vaccines.

05 Nov 2024·Microbiology spectrum

Mycobacterium tuberculosis VII secretion system effector molecule Rv2347c blocks the maturation of phagosomes and activates the STING/TBK1 signaling pathway to inhibit cell autophagy.

Article

Author: Abulikena, Yuerigu ; Jiang, Zhiyong ; Gao, Chaoyun ; Zhen, Junfeng ; Huang, Tingting ; Huang, Lingxi ; Xie, Jianping

The VII secretion system is the main channel for Mycobacterium tuberculosis (MTB) to secrete virulence proteins. The ESAT-like proteins EsxA/B and EsxW/V in the RD region of its genome have been used as targets for vaccine antigens. However, the function of EsxO/P has not been explored, although it was predicted to potentially induce Th1 cell responses as a vaccine development target. In this study, the VII secretion system effector molecule Rv2347c was heterologously expressed in Mycobacterium smegmatis and found to inhibit the expression of the early marker RAB5 of phagosomes, thus preventing the maturation process of phagosomes toward lysosomes, and activated the host cytoplasmic sensing pathway. It inhibited autophagy and activated IFNβ transcription through the STING/TBK1 pathway promoting the host's survival. Therefore, Rv2347c plays an important role in the pathogenesis of MTB with the potential to be utilized as a new target for tuberculosis vaccine development.IMPORTANCEWe found that the ESAT-like protein Rv2347c (EsxP) can inhibit the maturation of phagosomes, leading to mycobacterium escape from phagosomes into the cytoplasm, which triggers the host's cytoplasmic sensing pathway STING/TBK1, inhibiting autophagy and upregulating IFNβ transcription, which contributes to the survival of mycobacterium in the host cell. We also found that Rv2347c was able to activate host immunity by activating NF-κB via STING and promoting the transcription of downstream pro-inflammatory factors. Meanwhile, the host also produces IL-1β to repair phagosome maturation arrest via the STING-mediated non-NF-κB pathway.

01 Oct 2024·Indian Journal of Tuberculosis

Tuberculosis vaccine - A timely analysis of the drawbacks for the development of novel vaccines

Review

Author: Pusam, Yashika ; Jeyachandran, Dr Sivakamavalli

The BCG vaccine, Bacille Calmette Guerin, holds the distinction of being the most widely administered vaccine. Remarkably, a century has passed since its discovery; however, puzzlingly, questions persist regarding the effectiveness of the immune response it triggers. After years of diligent observation, it has been deduced that BCG imparts immunity primarily to a specific age group, namely children. This prompts a significant query: the rationale behind BCG's limited efficacy against TB in particular age groups and populations remains elusive. Beyond vaccinations, drug therapy has emerged as an alternative route for TB prevention. Nonetheless, this approach faces challenges in the contemporary landscape, marked by the emergence of new instances of MDR-TB and XDR-TB, compounded by the financial burden of treatment. It's noteworthy that BCG remains the sole WHO-approved vaccine for TB. This comprehensive review delves into several aspects, encompassing the immune response during infection, the shortcomings of BCG in conferring immunity, and the various factors contributing to its limitations. Within this discourse, we explore potential explanations for the observed deficiencies of the BCG vaccine and consider how these insights could catalyze the development of future vaccines. The current landscape of novel vaccine development for TB is illuminated, including a spotlight on the latest vaccine candidates.

100 Deals associated with Tuberculosis vaccine(Aeras Technologies LLC)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pulmonary Tuberculosis	Phase 2	-	National Institutes of Health	-
Pulmonary Tuberculosis	Phase 2	-	Crucell Holdings, Inc.	-
Pulmonary Tuberculosis	Phase 2	-	Aeras Technologies LLC	-
Tuberculosis	Phase 1	MZ	Aeras Global TB Vaccine Foundation	01 Sep 2010
Tuberculosis	Phase 1	KE	Aeras Global TB Vaccine Foundation	01 Sep 2010
Tuberculosis	Phase 1	ZA	Aeras Global TB Vaccine Foundation	01 Sep 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02414828 (Pubmed \| Pediatrics) Manual	Phase 2	Tuberculosis	72	AERAS-402	(ojladdgoon) = yshcmdhdan pjscwplnhp (fcdqvjqonj )	Positive	01 May 2017
				Placebo	(ojladdgoon) = qvmwyypwgc pjscwplnhp (fcdqvjqonj )
NCT02414828 (C-010-402, CTgov)	Phase 2	Pulmonary Tuberculosis	72	Placebo (Placebo)	rviqbsgvof(juqtmbhiqv) = grogmmeqee pdowdnpunm (mdfbthqufv, lrivcbrcdg - wmscbilqyp) View more	-	04 May 2016
				AERAS-402 3 x 10^8 vp (AERAS-402 3 x 10^8 vp)	rviqbsgvof(juqtmbhiqv) = hpmhinmppw pdowdnpunm (mdfbthqufv, agrtjmeuys - tzfofkxjug) View more
NCT01198366 (CTgov)	Phase 1/2	Tuberculosis	487	placebo (Dose Finding - Group 1)	nkvxytojnq(ylexyyilpm) = habaucqgyd fruciiawwc (kwtzjtfeap, prnohekzrc - lyeczhedie) View more	-	04 Aug 2015
				AERAS-402 (Dose Finding - Group 2)	nkvxytojnq(ylexyyilpm) = cdzjgiyzgf fruciiawwc (kwtzjtfeap, lixznpwung - ekjogxwrjw) View more
NCT01017536 (CTgov)	Phase 2	Tuberculosis \| HIV Infections	26	Placebo (Placebo)	nqkcxgslwn(lttkrflvwv) = wmxecffoim qpdczkwlae (otznxsusdb, klekrfvowq - iwywkgvuth) View more	-	13 Oct 2014
				AERAS-402 (Investigational Vaccine)	nqkcxgslwn(lttkrflvwv) = eqluyaznoo qpdczkwlae (otznxsusdb, tnnwtohvdy - eqejuzljok) View more