Campos Ivana B, Darrieux Michelle, Ferreira Daniela M, Miyaji Eliane N, Silva Débora A, Arêas Ana Paula M, Aires Karina A, Leite Luciana C C, Ho Paulo L, Oliveira Maria Leonor S
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil; Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
Microbes Infect. 2008 Apr;10(5):481-8. doi: 10.1016/j.micinf.2008.01.007. Epub 2008 Jan 20.
Strategies for the development of new vaccines against Streptococcus pneumoniae infections try to overcome problems such as serotype coverage and high costs, present in currently available vaccines. Formulations based on protein candidates that can induce protection in animal models have been pointed as good alternatives. Among them, the Pneumococcal Surface Protein A (PspA) plays an important role during systemic infection at least in part through the inhibition of complement deposition on the pneumococcal surface, a mechanism of evasion from the immune system. Antigen delivery systems based on live recombinant lactic acid bacteria (LAB) represents a promising strategy for mucosal vaccination, since they are generally regarded as safe bacteria able to elicit both systemic and mucosal immune responses. In this work, the N-terminal region of clade 1 PspA was constitutively expressed in Lactobacillus casei and the recombinant bacteria was tested as a mucosal vaccine in mice. Nasal immunization with L. casei-PspA 1 induced anti-PspA antibodies that were able to bind to pneumococcal strains carrying both clade 1 and clade 2 PspAs and to induce complement deposition on the surface of the bacteria. In addition, an increase in survival of immunized mice after a systemic challenge with a virulent pneumococcal strain was observed.
开发针对肺炎链球菌感染的新型疫苗的策略试图克服当前可用疫苗中存在的血清型覆盖范围和高成本等问题。基于能够在动物模型中诱导保护作用的蛋白质候选物的制剂已被视为很好的替代方案。其中,肺炎球菌表面蛋白A(PspA)在全身感染过程中发挥重要作用,至少部分是通过抑制补体在肺炎球菌表面的沉积,这是一种逃避免疫系统的机制。基于活重组乳酸菌(LAB)的抗原递送系统是黏膜疫苗接种的一种有前景的策略,因为它们通常被认为是安全的细菌,能够引发全身和黏膜免疫反应。在这项工作中,1型PspA的N端区域在干酪乳杆菌中组成性表达,并且将重组细菌作为黏膜疫苗在小鼠中进行测试。用干酪乳杆菌-PspA 1进行鼻腔免疫诱导了抗PspA抗体,这些抗体能够结合携带1型和2型PspA的肺炎球菌菌株,并诱导补体在细菌表面沉积。此外,观察到在用强毒肺炎球菌菌株进行全身攻击后,免疫小鼠的存活率有所提高。