Preclinical Evaluation of TB/FLU-04L—An Intranasal Influenza Vector-Based Boost Vaccine against Tuberculosis
Shurygina A.-P. Zabolotnykh N. Vinogradova T. Khairullin B. Kassenov M. Nurpeisova A. Sarsenbayeva G. Sansyzbay A. Vasilyev K. Buzitskaya J. Egorov A. Stukova M.
April 2023Multidisciplinary Digital Publishing Institute (MDPI)
International Journal of Molecular Sciences
2023#24Issue 8
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.
Ag85A , ESAT-6 , influenza vector , M. tuberculosis vaccine , mucosal immunization
Text of the article Перейти на текст статьи
Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, St. Petersburg, 197022, Russian Federation
Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation, St. Petersburg, 191036, Russian Federation
Research Institute for Biological Safety Problems, Gvardeiskiy, 080409, Kazakhstan
Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation
Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation
Research Institute for Biological Safety Problems
10 лет помогаем публиковать статьи Международный издатель
Книга Публикация научной статьи Волощук 2026 Book Publication of a scientific article 2026