Junqueira-Kipnis Ana Paula, de Castro Souza Carine, de Oliveira Carvalho Ana Carolina, de Oliveira Fabio Muniz, Almeida Vinnycius Pereira, de Paula Alisson Rodrigues, Celes Mara Rubia, Kipnis André
Department of Biosciences and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia 74605-050, Brazil.
Vaccines (Basel). 2022 Feb 16;10(2):306. doi: 10.3390/vaccines10020306.
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 (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.
大量潜伏性和活动性结核感染人群需要进一步努力研发新疫苗或改进卡介苗（BCG），卡介苗是唯一被批准用于预防该疾病的疫苗。在本研究中，我们开发了一种重组融合蛋白（PEPf），其包含来自结核分枝杆菌（Mtb）蛋白酶Rv0125、Rv2467和Rv2672的高密度免疫显性表位序列，该蛋白具有免疫原性，并用于开发表达该融合蛋白的重组卡介苗。用Mtb攻击后，引发了特异性免疫反应，导致肺部细菌载量降低，其保护能力与卡介苗相似。因此，卡介苗PEPf未能增强卡介苗所提供的保护作用。将PEPf与Advax4佐剂联合使用，并采用初免-加强策略作为亚单位疫苗进行测试。PEPf + Advax4在Mtb攻击后显著提高了保护作用，肺部细菌载量降低。我们的结果证实，Mtb蛋白酶可用于开发抗结核疫苗，并且在初免-加强方案后使用重组PEPf亚单位蛋白是增强卡介苗免疫的一种有前景的策略。
