Explained I New tuberculosis vaccine: why India waits with high hopes

Representative image Ctsy: Reuters

Hyderabad-based Bharat Biotech on Wednesday announced a strategic alliance with Biofabri, a Spanish biopharmaceutical company, to develop and manufacture a new vaccine for tuberculosis (TB), MTBVAC, for distribution in 70 countries with a high incidence of the disease.

This vaccine—which will enter phase 3 clinical trials in South Africa, Senegal, and Madagascar this year—if successful, will replace the Bacillus Calmette-Guérin (BCG) vaccine that has been in use for over 100 years and is offered to new-borns.

This news is of particular significance to India which reports more than 25 percent of all new TB cases and 34 percent of all TB deaths globally every year.

Over the last few years, drug-resistant and multi-drug-resistant TB, which are far more difficult and expensive to treat, have also emerged as a major public health challenge in the country.

In 2020, an estimated 1 crore people fell ill with TB globally, according to the World Health Organisation (WHO), while the 30 high TB burden countries, mainly in Southeast Asia and Africa, accounted for 86 percent of new TB cases.

That year, a total of 15 lakh people also died from the disease, including 2.14 lakh people with HIV, and the Stop TB Partnership estimates that an additional 14 lakh TB deaths will occur over the next four years due to developments stemming from COVID-19.

Current TB vaccine

The BCG vaccine is one of the most widely used of all current vaccines in the world and since 2004, about 10 crore children are vaccinated with BCG each year.

In infants, in addition to decreasing all-cause mortality, BCG confers protection, although not absolute, against the disseminated forms of the disease, miliary (a life-threatening type of TB that occurs when a large number of the bacteria travel through the bloodstream and spread throughout the body) and meningeal (meninges are the three membranes that cover the brain) tuberculosis.

However, in adolescents and adults, BCG’s efficacy is more variable, ranging from 0 to 80 percent in different parts of the world, depending on factors including socioeconomic conditions, HIV status, presence of environmental mycobacteria, or climate and air pollution.

A single dose of BCG vaccine is suggested to provide lifetime immunity, explained an official in India’s health ministry, and booster doses of BCG vaccine are not recommended by the WHO.

“But the vaccine has limited efficacy in preventing pulmonary TB in adults who, along with adolescents, are the biggest spreaders of the disease,” the official pointed out.

Despite BCG’s widespread use, TB remains the leading representative respiratory tract communicable disease.

And although incidence and mortality rates have slowly been declining since the turn of the 21st century, the WHO estimated 1 crore new cases and more than 14 lakh deaths reported at the global level in 2019.

The only other infectious disease in recent times that has surpassed TB in terms of the number of deaths has been COVID-19.

New vaccine on the block

As BCG is far from being a perfect vaccine against TB, there have been multiple efforts to develop better protection against the highly contagious disease. The global TB vaccine pipeline features 14 vaccine candidates in different stages of clinical development, from phase 1 through phase 3 clinical trials.

MTBVAC was designed and constructed between the late 1990s and early 2000s by scientists attached with the University of Zaragoza, Spain, and is based on live-attenuated mycobacterium tuberculosis, a key cause of TB in humans.

An urgent need to develop a vaccine was felt particularly in Spain after a deadly outbreak of multiple drug-resistant TB killed more than 100 HIV patients in the country in the early 1990s.

Also read: Bharat Biotech joins hands with BioFabri to develop, distribute a new TB vaccine MTBVAC

After rigorous pre-clinical studies, MTBVAC was tested in humans, both new-borns and adults, in South Africa and Switzerland beginning in 2012 and was found to be more effective against TB in both infants and adults.

Today Biofabri is the exclusive licensee and industrial and clinical developer of MTBVAC, and also a sponsor of the clinical trials.

In partnership with Tuberculosis Vaccine Initiative (TBVI), a US-based non-profit foundation, and MTBVAC intellectual owner University of Zaragoza, Biofabri has established two independent clinical development plans for intradermal MTBVAC.

The primary plan focuses on intradermal MTBVAC as a preventive vaccine administered in new-borns as part of the BCG replacement strategy.

The secondary plan, also in collaboration with US International AIDS Vaccine Initiative (IAVI), aims at the development of MTBVAC as a preventive vaccine in BCG-vaccinated adolescents and adults living in high-burden countries with or without prior infection with M. tuberculosis.

Bharat Biotech has opted for this vaccine candidate owing to its advanced stage of clinical development as well as the extremely promising results from phase 1 and phase 2 clinical trials, said Krishna Ella, company’s chairman and managing director in a statement on Wednesday.

India’s TB burden

TB is a major health problem for the country causing about 2.2 lakh deaths every year. In 2020, the government set a target to eliminate the disease but experts are doubtful whether the country is yet in a position to reduce the disease to the margins of India’s public health landscape.

Also read: Tuberculosis deaths on the rise again globally due to COVID-19: WHO

To make things worse, recently a new form of TB, Totally Drug-Resistant TB (TDR-TB) has also been discovered. This issue of drug resistance began with MDR-TB, moved to extremely drug-resistant TB (XDR-TB), and has now gone on to embrace the most dangerous form of the disease, TDR-TB.

Bharat Biotech said that a vaccine such as MTBVAC that prevents TB would be a big step to tackle the XDR/MDR-TB problem.