Lásaro Marcio O, Luiz Wilson B, Sbrogio-Almeida Maria E, Nishimura Lucilia S, Guth Beatriz E C, Ferreira Luis C S
Department of Microbiology, Biomedical Sciences Institute, University of São Paulo, Brazil.
Infect Immun. 2004 Nov;72(11):6480-91. doi: 10.1128/IAI.72.11.6480-6491.2004.
Repeated evidence has demonstrated that combined primer-booster immunization regimens can improve both secreted and humoral immune responses to antigens derived from viral, bacterial, and parasitic pathogens. For the present work, we evaluated the synergic serum immunoglobulin G (IgG) and fecal IgA antibody responses elicited in BALB/c mice who were intramuscularly primed with a DNA vaccine, pRECFA, followed by oral boosting with an attenuated Salmonella enterica serovar Typhimurium vaccine (HG3) strain, with both vaccines encoding the structural subunit (CfaB) of the CFA/I fimbriae produced by human-derived enterotoxigenic Escherichia coli (ETEC) strains. The immunological properties of the vaccine regimen were evaluated according to the order of the administered vaccines, the nature of the oral antigen carrier, the age of the vaccinated animals, the interval between the priming and boosting doses, and the amount of injected DNA. The production of gamma interferon and the IgG2a subclass in serum indicated that mice immunized with the primer-booster regimen developed prevailing type 1 T-cell-dependent immune responses. The synergic effect of the vaccine regimen on the induced antibody responses was also revealed by its ability to block the adhesive properties of CFA/I fimbriae expressed by live bacteria, as shown by the inhibition of Caco-2 cell and human erythrocyte binding. Moreover, DBA2 newborn mice were protected from lethal challenges with a CFA/I+ ETEC strain after the incubation of live bacteria with serum samples harvested from mice who were subjected to the primer-booster regimen. We propose, therefore, that the DNA primer-Salmonella booster regimen represents an alternative for the development of vaccines requiring both mucosal and systemic antibody responses for immunological protection.
反复的证据表明，联合初免-加强免疫方案可改善针对病毒、细菌和寄生虫病原体衍生抗原的分泌性免疫和体液免疫反应。在本研究中，我们评估了在BALB/c小鼠中引发的协同血清免疫球蛋白G（IgG）和粪便IgA抗体反应。这些小鼠先用DNA疫苗pRECFA进行肌肉内初免，随后用减毒鼠伤寒沙门氏菌疫苗（HG3）株进行口服加强免疫，两种疫苗均编码人源产肠毒素大肠杆菌（ETEC）菌株产生的CFA/I菌毛的结构亚基（CfaB）。根据所接种疫苗的顺序、口服抗原载体的性质、接种动物的年龄、初免和加强剂量之间的间隔以及注射DNA的量，评估了疫苗方案的免疫学特性。血清中γ干扰素和IgG2a亚类的产生表明，用初免-加强方案免疫的小鼠产生了主要的1型T细胞依赖性免疫反应。疫苗方案对诱导抗体反应的协同作用还通过其阻断活细菌表达的CFA/I菌毛黏附特性的能力得以体现，如对Caco-2细胞和人红细胞结合的抑制所示。此外，在用初免-加强方案处理的小鼠采集的血清样本与活细菌孵育后，DBA2新生小鼠受到CFA/I + ETEC菌株致死性攻击时得到了保护。因此，我们提出，DNA初免-沙门氏菌加强方案代表了一种开发需要黏膜和全身抗体反应以提供免疫保护的疫苗的替代方案。
