Department of Cell and Molecular Biology, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, Gujarat, India; B. R. D. School of Biosciences, Sardar Patel University, Vallabh Vidhyanagar, Gujarat, India.
Sardar Patel University, Vallabh Vidhyanagar, Gujarat, India.
Vaccine. 2019 May 21;37(23):3097-3105. doi: 10.1016/j.vaccine.2019.04.053. Epub 2019 Apr 29.
Shigellosis is an acute invasive disease of the lower intestine, which afflicts millions of people worldwide with an estimated one million fatalities per annum. Despite of extensive research during the last two decades, a vaccine against multi-drug resistant Shigella is not yet available in the market. To provide a safe, effective and broad-spectrum vaccine against Shigella, we explored food grade bacteria Lactococcus lactis (L. lactis) for the delivery of conserved antigenic protein; Outer membrane protein A (OmpA) to the mucosal sites for effective elicitation of systemic and mucosal immunity. We have previously confirmed the immunogenic potential of recombinant L. lactis expressing OmpA (LacVax® OmpA) in BALB/c mice. In the present study, we have characterized the humoral and cellular immune profile of LacVax® OmpA and assessed its protective efficacy using a newly developed human like murine shigellosis model. The significant increase in OmpA specific serum IgG, fecal sIgA and a Th1 dominant immune response (indicated by high INF-γ/IL-4 ratio) in LacVax® OmpA immunized mice revealed successful activation of humoral and cellular immunity. The LacVax® OmpA immunized animals were also protected from human-like shigellosis when challenged with S. flexneri 2a ATCC 12022. The antigen specific serum IgG, fecal sIgA, INF-γ and IL-10 levels were found to be the significant correlates of protection. Collectively these results suggest that the LacVax® OmpA is a promising prophylactic candidate against shigellosis. However, the protective efficacy of LacVax® OmpA in the higher animals would further strengthen its future application in humans.
志贺氏菌病是一种急性侵袭性下肠道疾病，全球估计每年有 100 万人因此死亡。尽管在过去二十年中进行了广泛的研究，但市场上仍没有针对多药耐药志贺氏菌的疫苗。为了提供针对志贺氏菌的安全、有效和广谱疫苗，我们探索了食品级细菌乳球菌（L. lactis），用于向黏膜部位传递保守抗原蛋白；外膜蛋白 A（OmpA），以有效引发系统和黏膜免疫。我们之前已经证实了表达 OmpA 的重组乳球菌（LacVax® OmpA）在 BALB/c 小鼠中的免疫原性。在本研究中，我们对 LacVax® OmpA 的体液和细胞免疫特征进行了表征，并使用新开发的类人鼠志贺氏菌病模型评估了其保护效力。 LacVax® OmpA 免疫小鼠的 OmpA 特异性血清 IgG、粪便 sIgA 和 Th1 优势免疫应答（高 IFN-γ/IL-4 比值）显著增加，表明体液和细胞免疫成功激活。 LacVax® OmpA 免疫动物在受到 S. flexneri 2a ATCC 12022 攻击时也能免受类人志贺氏菌病的侵害。抗原特异性血清 IgG、粪便 sIgA、IFN-γ 和 IL-10 水平被认为是保护的重要相关因素。总的来说，这些结果表明 LacVax® OmpA 是一种有前途的预防志贺氏菌病的候选疫苗。然而，LacVax® OmpA 在高等动物中的保护效力将进一步加强其在人类中的未来应用。
