Efficacy, Safety and Immunogenicity Evaluation of MTBVAC in Newborns in Sub-Saharan Africa

Summary

The objective of this project is to demonstrate safety, immunogenicity and improved efficacy of the new live attenuated M. tuberculosis vaccine called MTBVAC in a Phase 3 efficacy trial in HIV-uninfected infants born to HIV-infected and HIV-uninfected mothers as compared to standard of care BCG vaccination. The proposal builds upon a group of TB vaccine development partners in Europe and sub-Saharan Africa established in a previous EDCTP-supported project. It creates an expanded consortium of clinical trial partners for the optimal implementation of a large infant efficacy trial of MTBVAC in high TB incidence settings. New capacity for efficacy trials in infants will be a valuable resource for the TB vaccine development community. The proposal will create a network of institutions in three TB endemic African countries with enhanced laboratory capacity to conduct TB vaccine immunology studies and to bio-bank samples to discover immune correlates of vaccine-mediated protection.

Conditions

• Tuberculosis

Interventions

BIOLOGICAL

MTBVAC

MTBVAC is a novel TB vaccine candidate based on an attenuated M. tuberculosis clinical isolate of the Euro-American lineage. Attenuation is based on two independent, stable genetic deletions of the genes phoP and fadD26 coding for two major virulence factors, the transcription factor PhoP and the cell-wall lipids PDIM, respectively. We hypothesize that MTBVAC will provide improved protection, as individuals latently infected with live M.tuberculosis have an 80% lower chance of developing TB, and as MTBVAC contains most of the genes deleted from BCG and presents a wider collection of antigens to the host immune system. Preclinical studies in different animal models indicated that MTBVAC is safe and is able to induce an improved protection compared to BCG.

BIOLOGICAL

BCG

BCG is a live attenuated M. bovis strain developed 100 years ago and is used as a preventive vaccine against tuberculosis. It is administered at birth.

Sponsors & Collaborators

• TuBerculosis Vaccine Initiative

  collaborator OTHER

• University of Cape Town

  collaborator OTHER

• Institut Pasteur de Madagascar

  collaborator OTHER

• Biomedical Research Center EPLS

  collaborator OTHER

• Universidad de Zaragoza

  collaborator OTHER

• University of Stellenbosch

  collaborator OTHER

• University of KwaZulu

  collaborator OTHER

• Wits Health Consortium (Pty) Ltd

  collaborator OTHER

• Biofabri, S.L

  lead INDUSTRY

Principal Investigators

• Mark Hatherill · University of Cape Town, Faculty of Health Sciences

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

5 Minutes

Max Age

7 Days

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2022-10-17

Primary Completion

2029-02-28

Completion

2029-02-28

Countries

• South Africa

Study Locations