The Future of Tuberculosis Vaccines: Insights and Developments

In a world where infectious diseases are consistently battled against, Tuberculosis (TB) remains a formidable opponent. Despite the availability of the Bacillus Calmette-Guérin (BCG) vaccine, TB continues to be a major global health threat, with an estimated 1.3 million deaths and 10.6 million new cases in 2022. Furthermore, the increasing threat of drug-resistant TB underscores the urgent need for novel and effective TB vaccines. In this respect, a report by Mike Frick provides an overview of 17 TB vaccine candidates presently under research and development, with particular emphasis on those in Phase III trials. The report underscores the need for additional resources, especially from governments and industry, to support the development of these vaccines.

MTBVAC: A Promising Candidate

Among the vaccines under development, MTBVAC is a promising candidate currently undergoing various stages of trials. In an exciting development, IAVI and Zendal have announced funding for a Phase IIb trial of the TB vaccine candidate MTBVAC. The Bill and Melinda Gates Foundation has generously awarded IAVI US $55 million for this trial, with additional support from the German Federal Ministry of Education and Research. MTBVAC, the only live attenuated vaccine derived from Mycobacterium tuberculosis, the bacterium that causes TB disease in humans, has already shown favorable immunogenicity and safety profiles in previous studies.

Upcoming Trials

The trial is expected to enroll participants in mid-2024 and will be conducted on approximately 4,300 people with latent TB infection living in South Africa and other sub-Saharan African countries. The study aims to evaluate the safety and efficacy of MTBVAC in preventing TB disease in this population. If proven safe and effective, MTBVAC could be a significant tool in global strategies to suppress the TB pandemic.

In line with this, a Phase III trial of MTBVAC in neonates is already being conducted in South Africa, Madagascar, and Senegal with support from the European Developing Countries Clinical Trials Partnership. This marks a significant milestone as only a handful of TB vaccine candidate efficacy trials have ever been conducted.

Advancements in Vaccine Testing

Apart from the development of new vaccines, there are also advancements in the methods used to test TB vaccines. Researchers from Saint Louis University (SLU) have found a better way to test tuberculosis vaccines by using the BCG vaccine against tuberculosis administered to babies and small children to mimic the disease. This novel approach could predict how well a patient would respond to a vaccine scientists are developing. Furthermore, such human challenge trials can also reflect how men and women respond differently to viruses.

Challenges in Vaccine Development

While progress is encouraging, there have been setbacks in the race for a TB vaccine. The candidate Tuberculosis vaccine H56:IC31 has ended development based on early data from the Prevention of Recurrence (POR) TB Consortium. Although the vaccine was well tolerated and demonstrated immunogenicity, it did not provide protection against TB recurrence, leading to an increased rate of TB recurrence among its recipients as opposed to the placebo group. This highlights the immense challenges and complexities involved in TB vaccine development.

Despite these challenges, the concerted efforts of researchers, funding bodies, and governments worldwide give us hope in the fight against TB. With ongoing trials and continuous research, the landscape of TB vaccines is poised to change, bringing us closer to a world free from the threat of tuberculosis.