CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice
CpG DNA can induce strong Th1 humoral and cell-mediated immune responses against hepatitis B surface antigen in young mice
复制标题
DOI：
10.1073/pnas.95.26.15553
复制
发表时间：
1998-12-22
影响因子：
11.1
通讯作者：
Davis, HL
中科院分区：
文献类型：
--
作者：
Millan, CLB;Weeratna, R;Davis, HL
成功的新生儿免疫人类已被证明是困难的，我们已经评估了含CpG的寡核苷酸作为佐剂免疫年幼小鼠（1-14日龄）抗B病毒表面抗原。与DNA疫苗一样，蛋白质-明矾-CpG制剂在3或7日龄免疫的大多数小鼠中产生血清转化，而蛋白质-明矾或蛋白质-CpG制剂的血清转化率为0-10%。从新生儿到成年，所有动物用蛋白明矾疫苗免疫后均表现出强的Th 2样应答[主要是IgG 1，弱或不存在细胞毒性T淋巴细胞（CTL）]，在幼龄小鼠中用蛋白CpG也诱导了Th 2型应答（在1、3和7日龄小鼠中）和蛋白质-明矾-CpG（在1和3日龄小鼠中）进行免疫，但在更大年龄进行的免疫产生混合的Th 1/Th 2（Th 0）应答。DNA疫苗在1日龄和7日龄给药时产生Th 0样应答，在14日龄或成年小鼠中产生Th 1样应答（主要是IgG 2a和CTL）。令人惊讶的是，蛋白质-明矾-CpG制剂在血清转化百分比、出现速度和抗体应答的峰值滴度以及CTL的流行率和强度方面优于DNA疫苗。这些发现可能对人类婴儿的免疫具有重要意义。
Successful neonatal immunization of humans has proven difficult, We have evaluated CpG-containing oligonucleotides as an adjuvant for immunization of young mice (1-14 days old) against hepatitis B virus surface antigen. The protein-alum-CpG formulation, like the DNA vaccine, produced seroconversion of the majority of mice immunized at 3 or 7 days of age, compared with 0-10% with the protein-alum or protein-CpG formulations. All animals, from neonates to adults, immunized with the protein-alum vaccine exhibited strong T helper (Th)2-like responses [predominantly IgG1, weak or absent cytotoxic T lymphocytes (CTL)], Th2-type responses also were induced in young mice with protein-CpG (in 1-, 3-, and 7-day-old mice) and protein-alum-CpG (in 1- and 3-day-old mice) but immunization carried out at older ages gave mixed Th1/Th2, (Th0) responses. DNA vaccines gave Th0-like responses when administered at 1 and 7 days of age and Th1-like (predominantly IgG2a and CTL) responses with 14-day old or adult mice. Surprisingly, the protein-alum-CpG formulation was better than the DNA vaccine for percentage of seroconversion, speed of appearance, and peak titer of the antibody response, as well as prevalence and strength of CTL. These findings may have important implications for immunization of human infants.