Immunogenicity and Protective Efficacy of a Multi-Antigen <i>Mycobacterium tuberculosis</i> Subunit Vaccine in Mice
There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic <i>Mycobacterium tuberculosis</i> infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-08-01
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| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/12/9/997 |
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| Summary: | There is an urgent need for an effective TB vaccine capable of controlling both acute and chronic <i>Mycobacterium tuberculosis</i> infection in populations with diverse genetic backgrounds. In this study, we characterised the immunogenicity and protective efficacy of a novel protein-in-adjuvant subunit vaccine. The protein component is a fusion protein of three different <i>M. tuberculosis</i> antigens, which we termed CysVac5: CysD, a major component of the <i>M. tuberculosis</i> sulfate activation pathway that is highly expressed during the chronic stage of <i>M. tuberculosis</i> infection, is fused with two major secreted mycobacterial antigens, Ag85B and MPT83. Vaccination of C57BL/6 mice with CysVac5, formulated in a monophosphoryl lipid A (MPLA) and dimethyldioctadecylammonium (DDA) adjuvant combination, resulted in the potent generation of polyfunctional CD4<sup>+</sup> T cells secreting multiple cytokines, including IFN-γ, IL-2, TNF and IL-17, against each of the three components of the fusion protein. Furthermore, vaccination with CysVac5-MPLA/DDA conferred significant protection against infection in mouse lungs, which was greater than that afforded by BCG at extended time points post-challenge. The generation of antigen-specific and protective immunity was also observed in CysVac5 vaccinated BALB/c mice, indicating the vaccine could display efficacy across multiple genetic backgrounds. These results indicate that the CysVac5 vaccine has broad immunogenicity, is effective in controlling both acute and chronic phases of <i>M. tuberculosis</i> infection in mice, and warrants further investigation to assess its potential to control pulmonary TB. |
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| ISSN: | 2076-393X |