Gaillard María Emilia, Bottero Daniela, Zurita María Eugenia, Carriquiriborde Francisco, Martin Aispuro Pablo, Bartel Erika, Sabater-Martínez David, Bravo María Sol, Castuma Celina, Hozbor Daniela Flavia
Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT-CONICET La Plata, La Plata, Argentina.
Front Immunol. 2017 Sep 6;8:1099. doi: 10.3389/fimmu.2017.01099. eCollection 2017.
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 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, < 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 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.
通过百日咳疫苗接种及随后的母胎抗体转移实现的孕产妇安全已有充分记录,但关于此类抗体及后续疫苗接种对婴儿百日咳的保护作用的信息却很少。由于小鼠被广泛用于孕产妇疫苗接种研究,我们采用该模型来缩小我们对孕产妇百日咳免疫认识上的差距。因此,我们用商用无细胞百日咳(aP)疫苗对雌性小鼠进行免疫接种,并测量了后代在有无再次接种情况下抵御攻击的能力及特异性抗体水平。孕产妇免疫接种保护了后代免受百日咳感染,这种免疫保护转移至后代后可持续数周,16周龄后代肺部回收的菌落形成单位减少(4-5个对数,<0.001)即证明了这一点。此外,首次怀孕时通过孕产妇接种获得的免疫力在第四次怀孕时仍能为后代提供保护。在我们的实验方案条件下,aP诱导的免疫力对后代的保护作用通过胎盘和母乳喂养两种方式传递。过继转移实验表明,转移的抗体对后代检测到的保护作用比转移的全脾细胞更具决定性。与已报道的结果相反,在用相同或其他疫苗制剂对幼鼠进行疫苗接种后,转移的保护作用并未丧失,反之,母亲转移的免疫力也不干扰相同或不同疫苗对幼鼠接种所赋予的保护作用。这些结果表明,对怀孕雌性小鼠进行aP疫苗免疫接种可赋予保护性免疫力,该免疫力通过胎盘和母乳喂养传递给后代,同时不会影响后续幼鼠疫苗接种所增强的保护作用。这些结果——尽管诚然不一定能立即外推至人类——但仍使我们能够通过详细的采样和数据收集在可控条件下检验假设。这些发现有望完善假设,然后在后续的人体研究中进行验证。