Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 24, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/ijms24087439
Keywords
M; tuberculosis vaccine; Ag85A; ESAT-6; influenza vector; mucosal immunization
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Tuberculosis is a global health threat, and a new boost tuberculosis vaccine called TB/FLU-04L was developed. This vaccine uses an attenuated influenza A virus as a vector and encodes two mycobacterium antigens. Intranasal immunization with TB/FLU-04L induced a specific Th1 immune response and provided a level of protection comparable to BCG. Additionally, it significantly enhanced the protective effect of BCG in a prime-boost scheme.
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.
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