Ongoing clinical trial yields positive preliminary results for candidate tuberculosis (TB) vaccine M72/AS01E1.

The findings, published in The New England Journal of Medicine, show that M72/AS01E significantly reduced the incidence of pulmonary TB disease in HIV-negative adults who were already infected with latent TB at the time of vaccination. The results demonstrate an overall vaccine efficacy of 54%, with varied response rates observed in different demographic sub-groups.

The ongoing trial is conducted in TB-endemic regions in Kenya, South Africa and Zambia and involves 3,573 HIV-negative adults. For this analysis, participants who received two doses of either M72/AS01E or placebo 30 days apart have been followed for at least two years to detect evidence of pulmonary tuberculosis disease. Ten participants who received the vaccine developed active pulmonary tuberculosis compared to 22 participants in the placebo group.

The South African Tuberculosis Vaccine Initiative (SATVI) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa) – TB research groups based in the Institute of Infectious Disease & Molecular Medicine at the University of Cape Town – are two of 11 sites in Kenya, South Africa and Zambia where the study is conducted. The study is sponsored by the global healthcare company GSK, and conducted in partnership with Aeras, a nonprofit organisation dedicated to developing vaccines against TB.

A major task now will be to analyse samples collected from the trial to look for clues how we might do even better Professor Robert Wilkinson Professor in Infectious Diseases, Department of Medicine

TB is the leading cause of death through infectious disease worldwide and represents a significant public health threat with 1.6 million attributed deaths in 2016 globally. In South Africa, the estimated incidence of TB is 781 per 100,000 of the population. The World Health Organization estimates that one quarter of the global population has latent TB, with increasing prevalence of multi-drug resistant strains. Currently, there is no available TB vaccine with proven, consistent efficacy in adult populations.

“These results are a major advance for TB vaccine development, showing for the first time that a protein subunit vaccine can prevent progression to active TB disease in people who are already infected with latent TB at the time of vaccination,” said Professor Mark Hatherill, Director of SATVI.

“We are thrilled that a new generation TB vaccine candidate can prevent progression to active TB disease. This study lays the foundation for the next step, which is to determine what this protective immune response looks like so that we can improve TB vaccines even further,” said Associate Professor Thomas Scriba, Deputy Director (Immunology) of SATVI.

Professor Robert J Wilkinson of CIDRI-Africa, Imperial College London and the Francis Crick Institute London commented: “We are pleased to have had a large part in the conduct and analysis of this study. The results are intriguing and, overall, highly encouraging. A major task now will be to analyse samples collected from the trial to look for clues how we might do even better. Our previous experience and the combination of Crick and the Wellcome Centre in Cape Town uniquely positions us to play a significant role in this effort, at the same time as contributing to the development of scientific careers in Africa.”

The study is still ongoing and a final analysis including all efficacy, safety, reactogenicity and immunogenicity data will be performed in 2019 after all participants have completed three years of follow up.

‘Phase 2b Controlled Trial of M72/AS01E Vaccine to Prevent Tuberculosis’ by Olivier Van Der Meeren et al. is published in The New England Journal of Medicine.

This article was adapted from a joint press release by CIDRI-AFRICA & SATVI

Lead image credit: 'Pulmonary tuberculosis' by Yale Rosen [CC BY-SA 2.0  (https://creativecommons.org/licenses/by-sa/2.0)], via Wikimedia Commons