Bot A, Bot S, Garcia-Sastre A, Bona C
Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Viral Immunol. 1996;9(4):207-10. doi: 10.1089/vim.1996.9.207.
Lower responsiveness and higher susceptibility to tolerance are the two main characteristics of neonatal immunity that limit the efficacy of conventional vaccines administered during this period. Based on the fact that DNA immunization of adult organisms is able to generate protective immune responses, we investigated the ability of a plasmid-(NPV1) encoding nucleoprotein (NP) of A/PR8/34 strain of influenza virus to generate a cellular immune response following intramuscular delivery in neonates. Newborn mice immunized with NPV1 plasmid developed significant cytotoxic immunity, comparable to the immune response displayed by adult mice injected with the same dose of plasmid. Furthermore, mice infected with influenza virus 1 month after completion of immunization showed a significant decrease of virus lung titer between day 3 and 7 after challenge, consistent with the protectivity conferred by specific cytotoxic immunity. Thus, mice immunized as neonates with NPV1 plasmid developed a protective cellular immune response, like the adult mice. Therefore, the strategy of DNA immunization may be considered for the purpose of human vaccination to prevent horizontally and vertically transmitted life-threatening infections in infants or children.
低反应性和高耐受性易感性是新生儿免疫的两个主要特征,这限制了在此期间接种传统疫苗的效果。基于成年生物体的DNA免疫能够产生保护性免疫反应这一事实,我们研究了一种编码甲型流感病毒A/PR8/34株核蛋白(NP)的质粒(NPV1)在新生儿肌肉注射后产生细胞免疫反应的能力。用NPV1质粒免疫的新生小鼠产生了显著的细胞毒性免疫,与注射相同剂量质粒的成年小鼠所表现出的免疫反应相当。此外,免疫完成1个月后感染流感病毒的小鼠在攻毒后第3天至第7天病毒肺滴度显著下降,这与特异性细胞毒性免疫所赋予的保护作用一致。因此,用NPV1质粒作为新生儿免疫的小鼠产生了保护性细胞免疫反应,与成年小鼠一样。所以,为预防婴儿或儿童水平和垂直传播的危及生命的感染,DNA免疫策略可考虑用于人类疫苗接种目的。