A successful tuberculosis (TB) vaccine would have a major impact on morbidity and mortality associated with TB, and on global TB control. However, vaccine strategies have fallen short due to limited understanding of the types of Mycobacterium tuberculosis (Mtb) immunogens that induce long-term protective immunity. The design of an efficacious TB vaccine will also likely require formulation with appropriate vaccine adjuvants. Adjuvants not only induce potent immune responses that cannot be obtained with immunogens alone but are also responsible for driving distinct immune profiles that may be associated with protection against disease.
The National Institute of Allergy and Infectious Diseases (NIAID) recently awarded a contract to evaluate the development of novel TB vaccines. The AVAR-T program will provide up to 5-years of support to further the development of preventive, including post-exposure, TB vaccines through side-by-side comparisons of adjuvants in combination with Mtb immunogens, and to establish immunological profiles of adjuvants that work through different mechanisms, facilitating the identification of the most promising adjuvant:Mtb immunogen candidates for clinical development and potential immune correlates of protection.
The AVAR-T contract was awarded to The University of Sydney/Centenary Institute, and is led by Drs. Warwick Britton, Angelo Izzo and James Triccas. This program will examine early immune responses to Mtb after inoculation with different combinations of adjuvants comprised of Advax-CpG, Alhydroxiquim-II, and CAF01, and Mtb immunogens using preclinical animal models including in-depth phenotypic and functional immunological studies in combination with transcriptomic analyses. The studies will be complemented by in vitro studies in primary human and animal cells. Evaluation of the lead adjuvant:Mtb immunogen candidate will be conducted in non-human primates and in support of non-clinical investigational new drug-enabling studies. The AVAR-T program is designed to evaluate additional adjuvants that will be routed through the Mtb vaccine testing pipeline established by The University of Sydney/Centenary Institute.
Data generated from the AVAR-T studies is expected to be deposited into appropriate public databases such as ImmPort (https://www.immport.org/home), and the Vaccine Adjuvant Compendium (https://vac.niaid.nih.gov/).
Main Areas of Focus
- To further the development of preventive, including postexposure, TB vaccines through side-by-side comparisons of adjuvants in combination with Mtb immunogens
- To establish immunological profiles of adjuvants that work through different mechanisms, facilitating the identification of the most promising adjuvant-Mtb immunogen candidates for clinical development and potential immune correlates of protection