Barrios C, Brawand P, Berney M, Brandt C, Lambert P H, Siegrist C A
WHO Collaborating Centre for Neonatal Vaccinology, University of Geneva, Switzerland.
Eur J Immunol. 1996 Jul;26(7):1489-96. doi: 10.1002/eji.1830260713.
Induction of neonatal immune responses to vaccine antigens is believed to be of limited efficacy because of immune immaturity and particular susceptibility to tolerogenic signals during this period of life. To characterize particular features of neonatal immune responses to vaccine antigens, we assessed the capacity of BALB/c mice at different stages of immunological maturation to respond to a selection of vaccine antigens and presentation systems. Significant B and T cell responses to vaccine antigens (tetanus and measles virus peptides, tetanus toxoid, live viral attenuated measles virus, canarypox recombinant measles vector or bacillus Calmette-Guérin) were obtained as early as the first week of life. However, these neonatal responses differed qualitatively from adult responses by a decreased IgG2a/IgG1 ratio of vaccine-specific antibodies, the secretion of significantly higher interleukin-5 and lower interferon-gamma levels by vaccine-specific T cells and an impaired induction of cytotoxic T cell precursors. This pattern of biased Th2 versus Th1 responses induced upon early exposure to vaccines was not reversed by decreasing the doses of vaccine antigens. It did not disappear with aging and was still reflected in adult responses to booster immunization with the corresponding antigen. Thus, neonatal immunization can induce significant vaccine specific responses with a predominance of a Th2 pattern which can persist in boosted adult mice.
由于新生儿免疫不成熟且在此生命阶段对致耐受性信号特别敏感,人们认为新生儿对疫苗抗原的免疫反应诱导效果有限。为了表征新生儿对疫苗抗原免疫反应的特定特征,我们评估了处于免疫成熟不同阶段的BALB/c小鼠对一系列疫苗抗原和呈递系统作出反应的能力。早在出生后第一周就获得了对疫苗抗原(破伤风和麻疹病毒肽、破伤风类毒素、减毒活麻疹病毒、金丝雀痘重组麻疹载体或卡介苗)的显著B细胞和T细胞反应。然而,这些新生儿反应在质量上与成人反应不同,表现为疫苗特异性抗体的IgG2a/IgG1比值降低、疫苗特异性T细胞分泌的白细胞介素-5显著更高且干扰素-γ水平更低以及细胞毒性T细胞前体的诱导受损。早期接触疫苗后诱导的这种偏向Th2而非Th1反应的模式,不会因降低疫苗抗原剂量而逆转。它不会随着年龄增长而消失,并且在成人对相应抗原加强免疫的反应中仍然存在。因此,新生儿免疫可诱导显著的疫苗特异性反应,以Th2模式为主,这种模式可在成年小鼠加强免疫后持续存在。