Protease-Based Subunit Vaccine in Mice Boosts BCG Protection against Mycobacterium tuberculosis

Autor: Ana Paula Junqueira-Kipnis, Carine de Castro Souza, Ana Carolina de Oliveira Carvalho, Fabio Muniz de Oliveira, Vinnycius Pereira Almeida, Alisson Rodrigues de Paula, Mara Rubia Celes, André Kipnis
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Vaccines, Vol 10, Iss 2, p 306 (2022)
Druh dokumentu: article
ISSN: 10020306
2076-393X
DOI: 10.3390/vaccines10020306
Popis: The significant number of people with latent and active tuberculosis infection requires further efforts to develop new vaccines or improve the Bacillus Calmette-Guérin (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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