Miyaji E N, Dias W O, Gamberini M, Gebara V C, Schenkman R P, Wild J, Riedl P, Reimann J, Schirmbeck R, Leite L C
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
Vaccine. 2001 Dec 12;20(5-6):805-12. doi: 10.1016/s0264-410x(01)00395-4.
Streptococcus pneumoniae is one of the most important human pathogens and improvement of the currently used polysaccharide vaccines is being pursued. We constructed DNA vaccine vectors containing either the full-length psaA (pneumococcal surface adhesin A) or a truncated pspA (pneumococcal surface protein A--pspA') gene. Both constructs showed transient expression of the antigens in vertebrate cells and induced significant antibody response to the pneumococcal antigens in BALB/c mice injected intramuscularly (i.m.). Fusion with an N-terminal cytoplasmatic SV40 T-antigen (CT-Ag), which was previously shown to stabilize poorly expressed antigens through association with Hsp73, also induced anti-PspA antibody response. The induction of antibodies with a low IgG1:IgG2a ratio and elevated gamma interferon (IFN-gamma) production by spleen cells elicited by DNA vaccination indicate preferential priming of Th1 immunity. Since induction of antibodies against both PsaA and PspA was previously shown to correlate with protection against fatal infection with S. pneumoniae and cell-mediated immune responses could contribute to protection, further evaluation of PsaA and PspA as antigens for a DNA vaccine against S. pneumoniae could be promising.
肺炎链球菌是最重要的人类病原体之一，目前正在致力于改进现有的多糖疫苗。我们构建了包含全长psaA（肺炎球菌表面黏附素A）或截短的pspA（肺炎球菌表面蛋白A——pspA'）基因的DNA疫苗载体。两种构建体在脊椎动物细胞中均显示出抗原的瞬时表达，并在肌肉注射（i.m.）的BALB/c小鼠中诱导了对肺炎球菌抗原的显著抗体反应。与N端细胞质SV40 T抗原（CT-Ag）融合，先前已证明该抗原可通过与Hsp73结合来稳定低表达的抗原，也诱导了抗PspA抗体反应。DNA疫苗接种引发的低IgG1:IgG2a比值抗体的诱导以及脾细胞产生的γ干扰素（IFN-γ）升高表明Th1免疫的优先启动。由于先前已证明针对PsaA和PspA的抗体诱导与抵抗肺炎链球菌致命感染的保护作用相关，并且细胞介导的免疫反应可能有助于提供保护，因此将PsaA和PspA作为抗肺炎链球菌DNA疫苗的抗原进行进一步评估可能是有前景的。
