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Pertussis Maternal Immunization: Narrowing the Knowledge Gaps on the Duration of Transferred Protective Immunity and on Vaccination Frequency

机译:百日咳产妇的免疫接种:缩小关于转移性保护性免疫的持续时间和疫苗接种频率的知识差距

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摘要

Maternal safety through pertussis vaccination and subsequent maternal–fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP) vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4–5 logs, p < 0.001) in the colony-forming-units recovered from the lungs of 16-week-old offspring. Moreover, maternal-vaccination-acquired immunity from the first pregnancy still conferred protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results—though admittedly not necessarily immediately extrapolatable to humans—nevertheless enabled us to test hypotheses under controlled conditions through detailed sampling and data collection. These findings will hopefully refine hypotheses that can then be validated in subsequent human studies.
机译:通过百日咳疫苗接种和随后的母婴抗体转移的孕产妇安全性已有充分文献记载,但缺乏有关通过此类抗体和随后的疫苗接种对婴儿进行百日咳保护的信息。由于小鼠被广泛用于孕产妇疫苗接种研究,因此我们采用该模型来缩小我们对孕产妇百日咳疫苗免疫的了解的差距。因此,我们用市售无细胞百日咳(aP)疫苗给雌性小鼠接种疫苗,并测量了经过或未经过再疫苗接种的百日咳博德特氏菌挑战和特异性抗体水平的后代保护。产妇的免疫保护后代免受百日咳,这种免疫保护转移至后代可持续数周,这可以从16-位肺中回收的菌落形成单位减少(4-5 log,p logs <0.001)来证明。一星期大的后代。此外,从第一次妊娠获得的母体疫苗免疫仍然为后代直到第四次妊娠提供保护。在我们的实验方案的条件下,保护其后代不受aP诱导的免疫的影响既可以通过胎盘转移也可以通过母乳喂养。过继转移实验表明,转移的抗体比后代的整个脾细胞对检测后代的保护作用更大。与报告的发现相反,使用相同或其他疫苗制剂对婴儿小鼠进行疫苗接种后,转移的保护作用并未丢失,相反,从母亲转移的免疫力并未干扰通过对相同或不同疫苗进行婴儿疫苗接种所赋予的保护作用。这些结果表明,对怀孕的雌性小鼠进行aP-疫苗免疫可赋予保护性免疫,该保护性免疫既可经胎盘传递又可通过后代母乳喂养转移,而不会损害随后婴儿接种疫苗所加强的保护作用。这些结果(尽管不一定可以立即推断给人类)仍然使我们能够通过详细的采样和数据收集在受控条件下检验假设。这些发现有望有望完善这些假设,然后可以在随后的人体研究中对其进行验证。

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