Martinez X, Brandt C, Saddallah F, Tougne C, Barrios C, Wild F, Dougan G, Lambert P H, Siegrist C A
World Health Organization Collaborating Centre for Neonatal Vaccinology, Department of Pathology, University of Geneva, 1211 Geneva 4, Switzerland.
Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8726-31. doi: 10.1073/pnas.94.16.8726.
The relative deficiency of T helper type 1 (Th1) and cytotoxic T lymphocyte (CTL) responses in early life is associated with an increased susceptibility to infections by intracellular microorganisms. This is likely to reflect a preferential polarization of immature CD4 T cells toward a Th2 rather than a Th1 pattern upon immunization with conventional vaccines. In this report, it is shown that a single immunization within the first week of life with DNA plasmids encoding viral (measles virus hemagglutinin, Sendai virus nucleoprotein) or bacterial (C fragment of tetanus toxin) vaccine antigens can induce adult-like Th1 or mixed Th1/Th2 responses indicated by production of IgG2a vaccine-specific antibodies and preferential secretion of interferon-gamma (IFN-gamma) compared with interleukin (IL)-5 by antigen-specific T cells, as well as significant CTL responses. However, in spite of this potent Th1-driving capacity, subsequent DNA immunization was not capable of reverting the Th2-biased responses induced after early priming with a recombinant measles canarypox vector. Thus, DNA vaccination represents a novel strategy capable of inducing Th1 or mixed Th1/Th2 and CTL responses in neonates and early life, providing it is performed prior to exposure to Th2-driving conventional vaccine antigens.
生命早期1型辅助性T细胞（Th1）和细胞毒性T淋巴细胞（CTL）反应的相对不足与细胞内微生物感染易感性增加有关。这可能反映出在用传统疫苗免疫时，未成熟的CD4 T细胞优先向Th2而非Th1模式极化。在本报告中，研究表明，在生命的第一周内用编码病毒（麻疹病毒血凝素、仙台病毒核蛋白）或细菌（破伤风毒素C片段）疫苗抗原的DNA质粒进行单次免疫，可诱导产生成人样的Th1或混合Th1/Th2反应，表现为产生IgG2a疫苗特异性抗体，抗原特异性T细胞分泌干扰素-γ（IFN-γ）相较于白细胞介素（IL）-5更为优先，以及显著的CTL反应。然而，尽管具有这种强大的Th1驱动能力，但后续的DNA免疫并不能逆转在用重组麻疹金丝雀痘病毒载体进行早期致敏后诱导的Th2偏向性反应。因此，DNA疫苗接种代表了一种能够在新生儿期和生命早期诱导Th1或混合Th1/Th2以及CTL反应的新策略，前提是在接触Th2驱动的传统疫苗抗原之前进行。
