What do we need to accelerate the pace of development of the more than 14 vaccine candidates against this disease that are in clinical trials?
It is estimated that the covid-19 pandemic has caused more than 6 million deaths in the last two years. The research and development of vaccines against this disease has achieved an unprecedented milestone. In record time, several vaccines were developed, studied for safety and efficacy, and approved for use.
For its part, it is estimated that tuberculosis, a disease treatable with antibiotics, has caused the death of more than 1,000 million people in the last 200 years. The bacterium Mycobacterium tuberculosis was described by Robert Koch in 1882 as the cause of this pathology. However, for more than 100 years we have had a single vaccine that, moreover, does not work against the respiratory forms of the disease.
Today tuberculosis continues to cause more than 1.5 million deaths a year, a figure only surpassed (among infectious diseases) by the coronavirus in 2020 and 2021. These figures, together with the increase in forms resistant to treatment, make the Research for new effective vaccines against transmissible forms of tuberculosis is more urgent and necessary than ever.
Two vaccines at very different speeds
The covid-19 pandemic is estimated to have set back progress in the global fight against tuberculosis by about 12 years. The latest WHO report concludes that in 2020, for the first time in a decade, cases of this disease stopped falling worldwide. And what is more serious, its diagnosis and treatment has decreased, with which we expect a rebound in infections and deaths from tuberculosis in the coming years.
In this context, what is most worrying are the cases of multidrug-resistant tuberculosis that cause us to lose the ability to treat the disease and return to the pre-antibiotic era. If this happens, given that it is transmitted by the respiratory route, we could have drug-resistant tuberculosis pandemics in the future that are originating in countries with a high incidence of the disease and treatment failures.
According to the STOP-TB organization, public investment in tuberculosis vaccines in 2019 was in the order of one dollar for every $1,000 of public-private investment in coronavirus vaccines in 2021.
This investment in immunization against SARS-CoV-2 has made it possible that by 2022 we will have nine vaccines validated by the WHO for emergency use and that another 149 candidates are already in clinical trials.
For the first covid-19 vaccines, the time between their development and authorization did not last even a year. During this period, clinical trials were carried out to determine its safety and immunogenicity and its safety and efficacy were verified.
Tuberculosis vaccines in clinical trials
The only currently licensed vaccine against tuberculosis is BCG. This has more than 100 years of use for its protection against severe forms in children and the reduction of infant mortality. It is one of the most widely used vaccines worldwide, but it confers very poor protection against the transmissible respiratory forms of the disease.
BCG or bacillus Calmette-Guérin derives from a strain of Mycobacterium bovis, which caused tuberculosis in cows. Today, 14 tuberculosis vaccine candidates are in clinical trials. One of these candidates is the Spanish MTBVAC (for Mycobacterium tuberculosis vaccine).
The long development of MTBVAC
Among the 14 tuberculosis vaccine candidates, MTBVAC is the only one based on the pathogen Mycobacterium tuberculosis isolated from humans. We have developed it at the University of Zaragoza with the support of different research framework programs of the European Union.
In the more than 25 years of research and development of this Spanish vaccine (in collaboration with a large number of international research centers) we have verified that it shows an attenuation similar to BCG, but protects better than the latter in different animal models.
Since 2008, the University of Zaragoza has had an industrial partner, the biopharmaceutical company Biofabri. She is responsible for the industrial and clinical development of MTBVAC.
In 2012, the clinical development of the vaccine began with a phase 1 for the study of safety and immunogenicity in adults in Switzerland. Also, in 2015, another phase 1 safety and immunogenicity study in newborns was conducted in South Africa. For now, a phase 2 in adults and another phase 2 in newborns have also been completed in South Africa.
After 10 years of clinical research, the Spanish vaccine is going to start phase 3 studies in approximately 7,000 babies in Senegal, Madagascar and South Africa in 2022. Thus, the efficacy will be analyzed in different centers during the years of the project, partially financed by the European Union through the EDCTP program and by Biofabri.
It will be done thanks to the collaboration of international organizations such as TBVI and IAVI, as well as the recent agreement between the companies Biofabri and Bharat Biotech, in India. These agreements seek to ensure the distribution of the vaccine in more than 70 countries in Southeast Asia and sub-Saharan Africa with a high incidence of tuberculosis, including India, which declares more than 25% of cases worldwide.
Why do we need to speed up the process?
All of these organizations join forces with the challenge of seeking funding and designing MTBVAC efficacy studies in tens of thousands of adolescents and adults where transmissible forms of pulmonary tuberculosis are most prevalent. The objective is to be able to accelerate its use in the population that needs it most.
Tuberculosis can be cured with a combination of drugs for 6 months. We have to be aware that it is a respiratory and communicable disease. If we fail to control it worldwide with an effective vaccine against respiratory forms, the threat of an epidemic of untreatable strains will always be present.
If it has been possible to carry out the efficacy studies for covid-19 in record time, we think that it is also possible to accelerate these studies of the most advanced tuberculosis vaccines and have new ones that can help us control them in the near future. .
This article has been published inThe Conversation