Journal
VACCINES
Volume 10, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/vaccines10020306
Keywords
tuberculosis; subunit vaccine; PepN; PepA; Mtb32a; Msh1; recombinant BCG; adjuvant; Advax4
Categories
Funding
- National Council for Scientific and Technological Development-CNPq, Brazil [303671/2019-0, 314366/2020-2, 421867/2018-3, 406868/2016-6]
- CAPES-Coordenacao de Apefeicoamento de Pessoal de Nivel Superior, Brazil [001]
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A new tuberculosis vaccine PEPf was developed, which can reduce lung bacterial load and improve protection. Combining PEPf with the Advax4 adjuvant and using a prime-boost strategy as a subunit vaccine significantly enhances protection.
The significant number of people with latent and active tuberculosis infection requires further efforts to develop new vaccines or improve the Bacillus Calmette-Guerin (BCG), which is the only approved vaccine against this disease. In this study, we developed a recombinant fusion protein (PEPf) containing high-density immunodominant epitope sequences from Rv0125, Rv2467, and Rv2672 Mycobacterium tuberculosis (Mtb) proteases that proved immunogenic and used it to develop a recombinant BCG vaccine expressing the fusion protein. After challenging using Mtb, a specific immune response was recalled, resulting in a reduced lung bacterial load with similar protective capabilities to BCG. Thus BCG PEPf failed to increase the protection conferred by BCG. The PEPf was combined with Advax4 adjuvant and tested as a subunit vaccine using a prime-boost strategy. PEPf + Advax4 significantly improved protection after Mtb challenge, with a reduction in bacterial load in the lungs. Our results confirm that Mtb proteases can be used to develop vaccines against tuberculosis and that the use of the recombinant PEPf subunit protein following a prime-boost regimen is a promising strategy to improve BCG immunity.
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