Vaccines

Need for effective TB vaccines

There is a critical need for new TB vaccines that are more effective than the Bacille Calmette-Guérin (BCG) vaccine in preventingpulmonary as well as extra pulmonary forms of TB in all age groups. The BCG vaccine, which is now over 100-years old, has been shown to be immunoprotective against extra pulmonary forms of TB in children, including TB meningitis. However, the protection provided against pulmonary TB in adults is variable. New vaccines are also required keeping in view the slow decline in TB incidence globally and the persistent threat of MDR-TB.

The pipeline of vaccine includes recombinant BCGs, whole-cell derived vaccines, recombinant viral-vectored platforms, protein and adjuvant combinations, and mycobacterial extracts. For instance, sixteen different TB vaccine candidates are currently in clinical trials globally, with a handful approaching or currently in proof-of concept (Phase IIb) studies in the field, and many more in preclinical development. There are currently eight vaccines in Phase II or Phase III trials.These vaccines aim either to prevent infection (pre-exposure) or to prevent primary progression to disease or reactivation of Latent TB Infection(LTBI -post-exposure,). These would have a critical role in India’s fight against TB.

All vaccine research undergoing in different Indian academic labs will be evaluated and promising vaccine leads will be developed further to advance through manufacturing, toxicity and clinical trials.

Role of ITRC

ITRC will help design, conduct and validate new vaccine candidates in India. Itwill also support the development of indigenous vaccine candidates through institutional collaboration and funding.

Objectives

• To establish the role of host immune response to eliminate infection and disease.
• To identify vaccines in most advanced stage of early development.
• To take them forward through clinical trials for prevention of infection and disease.
• Develop and standardize protocols and SOPs for clinical trials.
• To undertake immunological/molecular/genetics/biopharma research domestically and through international collaboration.
• To establish an environment conducive for clinical research and existing vaccine candidate trials.
• To develop an appropriate infrastructure to support clinical vaccine trials and assure enrolment of sufficient numbers of people to address immunological responses that may vary by region and settings.
• To identify suitable biomarkers for use in clinical trials to measure correlates of protection

Deliverables

• An efficacious anti-relapse TB vaccine (5 years)
• An efficacious TB preventative vaccine (10 years)

Progress So Far

The vaccine candidates under clinical development by different manufacturers will beevaluated for immunogenicity and efficacy in the Indian population. Based on the different clinical end points various TB vaccines with different targets/ clinical end-points will need to be evaluated in Indian population and these are:

• Vaccine to boost BCG vaccine to prevent infection (Prevention of Infection -POI)
• Vaccine to boost BCG to prevent disease (Prevention of disease -POD)
• Therapeutic vaccine to decrease treatment duration
• Vaccine to prevent recurrence post-treatment

The landscaping of TB vaccines has identified three vaccine candidates which can be tested for different end points in the immediate future.

The three vaccines identified are:

• VPM1002: Live recombinant vaccine from the Serum Institute, India
• ID93/ GLA-SE: Arecombinant protein vaccine, discovered by Infectious Disease Research Institute , Seattle and licensed to GennovaBiopharmaceuticals, India
• M72/ AS01: A recombinant protein vaccine by GSK, Belgium
• MIP
• DAR 901

Depending on the clinical end point of the vaccine, different target populations will have to be recruited in various clinical trials to test respective vaccine efficacy.Investigational New Dossiers (IND) will be submitted to regulatory authorities for approval by Drug Controller General of India. All investigational vaccines will be released by CRI, Kasauli after testing and trial site ethics committee will approve participation of each site.

Click here to view the Vaccines Research Portfolio

ITRC: India TB Research Consortium