Department of Microbiology and Cell Biology, Centre for Infectious Disease Research and Biosafety Laboratories, Indian Institute of Science, Bangalore, India.
PLoS One. 2010 Feb 10;5(2):e9139. doi: 10.1371/journal.pone.0009139.
Pregnancy is a transient immuno-compromised condition which has evolved to avoid the immune rejection of the fetus by the maternal immune system. The altered immune response of the pregnant female leads to increased susceptibility to invading pathogens, resulting in abortion and congenital defects of the fetus and a subnormal response to vaccination. Active vaccination during pregnancy may lead to abortion induced by heightened cell mediated immune response. In this study, we have administered the highly attenuated vaccine strain DeltapmrG-HM-D (DV-STM-07) in female mice before the onset of pregnancy and followed the immune reaction against challenge with virulent S. Typhimurium in pregnant mice. Here we demonstrate that DV-STM-07 vaccine gives protection against Salmonella in pregnant mice and also prevents Salmonella induced abortion. This protection is conferred by directing the immune response towards Th2 activation and Th1 suppression. The low Th1 response prevents abortion. The use of live attenuated vaccine just before pregnancy carries the risk of transmission to the fetus. We have shown that this vaccine is safe as the vaccine strain is quickly eliminated from the mother and is not transmitted to the fetus. This vaccine also confers immunity to the new born mice of vaccinated mothers. Since there is no evidence of the vaccine candidate reaching the new born mice, we hypothesize that it may be due to trans-colostral transfer of protective anti-Salmonella antibodies. These results suggest that our vaccine DV-STM-07 can be very useful in preventing abortion in the pregnant individuals and confer immunity to the new born. Since there are no such vaccine candidates which can be given to the new born and to the pregnant women, this vaccine holds a very bright future to combat Salmonella induced pregnancy loss.
妊娠是一种短暂的免疫抑制状态,它的进化是为了避免母体免疫系统对胎儿的免疫排斥。孕妇改变的免疫反应导致对入侵病原体的易感性增加,导致流产和胎儿先天缺陷以及对疫苗接种的反应异常。怀孕期间进行主动免疫接种可能会导致由增强的细胞介导免疫反应引起的流产。在这项研究中,我们在怀孕前给雌性小鼠接种了高度减毒的疫苗株 DeltapmrG-HM-D(DV-STM-07),并在怀孕小鼠中对其进行了毒力 S. Typhimurium 攻击后的免疫反应进行了跟踪。我们证明 DV-STM-07 疫苗可在怀孕小鼠中预防沙门氏菌感染,并防止沙门氏菌引起的流产。这种保护是通过引导免疫反应向 Th2 激活和 Th1 抑制方向发展来实现的。低 Th1 反应可防止流产。在怀孕前使用活减毒疫苗存在传播给胎儿的风险。我们已经表明,该疫苗是安全的,因为疫苗株会很快从母体中消除,不会传播给胎儿。该疫苗还赋予了接种母亲的新生小鼠免疫力。由于没有证据表明疫苗候选物到达了新生小鼠,我们假设这可能是由于保护性抗沙门氏菌抗体的跨初乳转移。这些结果表明,我们的疫苗 DV-STM-07 可非常有效地预防孕妇流产,并赋予新生儿免疫力。由于没有可以给新生儿和孕妇使用的此类疫苗候选物,因此该疫苗在预防沙门氏菌引起的妊娠丢失方面具有非常光明的前景。