Update on Tuberculosis containment using vaccine – Taming the disease

By Ajay V. Patil

The epidemiological menace of Tuberculosis (TB)

Tuberculosis now surpasses HIV and Malaria infections worldwide with 10.4 million new cases and 1.7 million deaths annually. This also includes 0.4 million deaths in people with HIV infection (1). In such dire straits, WHO developed ‘End TB Strategy’ with an ambitious goal of reducing the 90% incidence of tuberculosis disease by 2035. But on the ground, there is only reduction in TB mortality rate (decline by 30% since year 2000) and slight decrease in incidence (1-2% per year). Incidence of drug-resistant disease is also rising to add the burden.

Challenges in TB vaccine development for protection against disease

In most infectious diseases, vaccines are considered as most effective and economical interventions for protection against the disease. TB disease is historically known for posing difficult challenge in using vaccination to contain disease development. Mainly, detailed knowledge of immunologic mechanisms for protection against tuberculosis is vital, given that the disease develops in only 5 to 10% of patients infected with M. tuberculosis. However, immunodeficiency increases this risk to approximately 8% per year. Other important argument is the conflicting reports of British Medical Research Council trial with BCG vaccine in adolescents (87% protective against disease and 74% protective at 20 years) and the largest 15 years long BCG vaccine trial, with 260,000 people in India (no protection in any age group). Prior exposure to M. tuberculosis or nontuberculous mycobacteria in Indian population, was reported to cause the interference in the detection of any additional protection provided by the vaccine in this case. There were more disappointing attempts in this quest for better vaccination against TB.

M72/AS01_E vaccine Phase IIb results – new hope in the pipeline

However recently published study by Van Der Meeren and group showed significant efficacy in the prevention of clinical tuberculosis by a subunit vaccine, M72/AS01_E, among people already infected with M. tuberculosis. This vaccine has two M. tuberculosis proteins with AS01_E adjuvant. The primary end point was, ‘preventing active pulmonary tuberculosis in adults’ who had received the BCG vaccine as children in almost all the cases. The trial was conducted in about 3500 adults in 11 centers in South Africa, Kenya, and Zambia. The overall vaccine efficacy was 54% (achieved proof of principle). Interestingly, protection was greater in 25 years of age or younger participants than older participants. Also, men were found to benefit more than women. The role of adjuvant AS01_E is assumed to be critical in this trial (same adjuvant used in malaria vaccines).

Envisioning future – research and access

Detailed understanding of immunologic and expression profile differences between recipients who were protected and those who were not can plausibly validate this vaccine as ‘proof of concept’. ‘Durability of protection’ and ‘need for revaccination’ are also important determining factors in this case. Further, phase III trial in multiple geographic populations will be an important cornerstone for such vaccine considering the epidemiology of infection. Once validated through the scientific and clinical timelines there are additional challenges to facilitate the affordable access worldwide (considering 95% incidence in low-and-middle-income countries).

References

1. https://www.nejm.org/doi/full/10.1056/NEJMe1812483?query=featured_secondary
2. https://www.nejm.org/doi/10.1056/NEJMoa1803484

Author

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