1. Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis.
- Author
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Shurygina, Anna-Polina, Zabolotnykh, Natalia, Vinogradova, Tatiana, Khairullin, Berik, Kassenov, Markhabat, Nurpeisova, Ainur, Sarsenbayeva, Gulbanu, Sansyzbay, Abylai, Vasilyev, Kirill, Buzitskaya, Janna, Egorov, Andrey, and Stukova, Marina
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TUBERCULOSIS , *TUBERCULOSIS vaccines , *INFLUENZA , *BCG vaccines , *VACCINE effectiveness , *CHIMERIC proteins - Abstract
Tuberculosis is a major global threat to human health. Since the widely used BCG vaccine is poorly effective in adults, there is a demand for the development of a new type of boost tuberculosis vaccine. We designed a novel intranasal tuberculosis vaccine candidate, TB/FLU-04L, which is based on an attenuated influenza A virus vector encoding two mycobacterium antigens, Ag85A and ESAT-6. As tuberculosis is an airborne disease, the ability to induce mucosal immunity is one of the potential advantages of influenza vectors. Sequences of ESAT-6 and Ag85A antigens were inserted into the NS1 open reading frame of the influenza A virus to replace the deleted carboxyl part of the NS1 protein. The vector expressing chimeric NS1 protein appeared to be genetically stable and replication-deficient in mice and non-human primates. Intranasal immunization of C57BL/6 mice or cynomolgus macaques with the TB/FLU-04L vaccine candidate induced Mtb-specific Th1 immune response. Single TB/FLU-04L immunization in mice showed commensurate levels of protection in comparison to BCG and significantly increased the protective effect of BCG when applied in a "prime-boost" scheme. Our findings show that intranasal immunization with the TB/FLU-04L vaccine, which carries two mycobacterium antigens, is safe, and induces a protective immune response against virulent M. tuberculosis. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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