A study of tuberculosis in macaque models shows that the new vaccine MTBVAC created by the University of Zaragoza offers better protection than the current BCG vaccine.

From left to right Nacho Aguiló (University of Zaragoza) and the authors: of the article Sally Sharpe (Public Health England), study coordinator, Andrew White (Public Health England) First author and Eugenia Puentes (Biofabri, Zendal Group)
  • According to the results published in the vaccines journal NPJ of the group Nature, MTBVAC is more efficient against aerosol exposure infection to Mycobacterium tuberculosis. They support it as a candidate for universal vaccination against tuberculosis and an alternative to the current vaccine
  • The development of this vaccine will be carried out alongside the Spanish biopharmaceutical company Biofabri which belongs to Zendal Group, as an industrial partner responsible for the clinical and industrial development of MTBVAC

Porriño, Wednesday the 13th of January 2021. The new tuberculosis vaccine MTBVAC, created by the University of Zaragoza and developed by its industrial partner, the pharmaceutical company Biofabri, takes a new step as a candidate for universal vaccination against TB and an alternative to the current vaccine (BCG), according to the results of the research published in the vaccines journal Nature Publishing Group Vaccines (NPJ-Vaccines) of the group Nature (DOI: 10.1038/s41541-020-00262-8).

The article shows the results of a study carried out by researchers from Europe and the United States about protection of the MTBVAC compared to the current BCG vaccine in a respiratory tuberculosis model in rhesus macaques. This study shows more efficiency and consequently better protection from the MTBVAC vaccine against aerosol infection with Mycobacterium tuberculosis when compared to the current BCG vaccine and this article supports it as a candidate for universal vaccination against tuberculosis and an alternative to the current vaccine.

The study published on 4th of January, by the scientific journal NPJ-Vaccines consolidates previous preclinical and clinical studies on safety and immunogenic profiles and offers favourable proof of concept tests on the efficiency of MTBVAC in a macaque model, the most relevant in efficiency against respiratory tuberculosis. It supports and urges the clinical development of studies to demonstrate the efficiency of MTBVAC as a prophylactic vaccine against respiratory TB in humans, which would turn MTBVAC into an essential tool in the fight against TB.

The group of Mycobateria Genetics of the University of Zaragoza have worked for over twenty years on the development of the MTBVAC vaccine. It is led by Aragon professor Carlos Martín, who belongs to the Biomedical Research Network Centre CIBER for respiratory illnesses of the Carlos III Healthcare Institute, affiliated the Healthcare Research Institute of Aragon Region (IIS-Aragón).

The leading cause of death by infectious diseases in the world, only surpassed in the year 2020 by COVID-19

Despite the WHO’s 1993 declaration on tuberculosis being a “Global emergency”, today the illness continues to be one of the main causes of death by infectious disease in the world. The WHO report of 2020 estimates that 1.4 million people died from tuberculosis in 2019 and it estimates that as a consequence of the COVID-19 pandemic, the deaths from TB might increase by up to 20% in the next 5 years.

The current BCG vaccine, based on a live attenuated form of Mycobacterium bovis isolated from cows and which was first used in humans as a tuberculosis vaccine 100 years ago, continues to be the only licensed vaccine against the disease. After decades of research in this field, MTBVAC is the first and only vaccine based on the human attenuated pathogen M. tuberculosis that has entered human clinical evaluation, a historic milestone in human vaccinology. MTBVAC has demonstrated a favourable safety profile in Phase 1A studies of adults in Switzerland and in Phase 1B of newborns in South Africa where they are currently developing studies in Phase 2A in healthy newborns and TB infected and uninfected adults to allow for dose selection and study its safety and immunogenicity profile with a larger group of participants.

The article by White et al., led by Dr Sally Sharpe (Public Health England) shows that a single dose of the MTBVAC vaccine administered intradermally confers significantly better protection against aerosol exposure to M. tuberculosis when compared to BCG at the same dose and administration method. Vaccination by MTBVAC resulted in significant reduction in disease pathology induced by M. tuberculosis infection as measured by medical scan imaging in vivo, macroscopic pathological lesions examinations and pathological anatomy study of the frequency and severity of pulmonary granulomas.

The publication shows for the first time the immune response induced after vaccination with MTBVAC in macaques and compares them with the immunological patterns studied in the previous human trials, in Phase 1A in adults (Spertini et al Lancet Respiratory Medicine 2015) and in Phase 1B in infants (Tameris et al Lancet Respiratory Medicine 2019), as well as in the ongoing Phase 2A trials in adults (NCT02933281) and in Phase 2A infants (NCT03536117). The results show that the immunological profiles induced after vaccination with MTBVAC and BCG reflect those identified in human clinical trials of MTBVAC.

The production of specific T-cell cytokines following stimulation with MTBVAC and M. tuberculosis peptide combination revealed a predominantly Th1 response of multifunctional CD4 T cells (IFN-γ + TNF-α + IL2 +). T-cell populations were detected in which the secretion of specific IFN-γ increased following stimulation with CFP10 protein (present in MTBVAC and absent in the current BCG vaccine), confirming our previous studies in mouse models that showed a correlation of protection with CFP10-specific response (Aguilo et al Nature Communications 2017). These results, added to those recently published by the team at the University of Zaragoza in a mouse model (Pérez et al EBioMedicine 2020), indicate that MTBVAC constructed from a clinical strain belonging to lineage 4, the most frequently transmitted lineage in Europe, Africa and America, also protects against the M. tuberculosis lineages 2, 3 and 4, which are the most widespread strains throughout the world, including Asia, allowing to anticipate good protection of MTBVAC against the main strains of M. tuberculosis circulating globally. Recent publications of the group indicate that MTBVAC confers a nonspecific immunity in human monocytes similar to that conferred by BCG, also called “trained immunity”, as well as protection against pneumococcal pneumonia in mouse model (Tarancon et al. Plos Pathogens).

Link to the article in NATURE MAGAZINE: