Laboratorio VacSal, Instituto de Biotecnología y Biología Molecular (IBBM), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CONICET, La Plata, Argentina.
Front Immunol. 2023 Jun 26;14:1192119. doi: 10.3389/fimmu.2023.1192119. eCollection 2023.
With the introduction of pertussis immunization for pregnant women in many countries, there has been renewed interest in the impact of whole-cell pertussis vaccine (wP) versus acellular vaccine (aP) on disease control, particularly regarding the best approach for priming. To gather evidence on this topic, we analyzed the impact of aP or wP priming on aP vaccination during pregnancy (aPpreg) in mice. Two-mother vaccination schemes were employed (wP-wP-aPpreg and aP-aP-aPpreg), and the immune response in the mothers and their offspring, as well as the protection of the offspring against challenge, were assessed. Pertussis toxin (PTx)-specific IgG responses were detected in mothers after both the second and third doses, with higher titers after the third dose, regardless of the vaccination schedule. However, a significant reduction in PTx-IgG levels was observed after 22 weeks post aPpreg immunization in mothers with the aP-aP-aPpreg scheme but not in the wP-wP-aPpreg immunized mothers. The aP-aP-aPpreg schedule triggered a murine antibody response mainly to a Th2-profile, while wP-wP-aPpreg induced a Th1/Th2 mixed profile. Both immunization schemes administered to the mothers protected the offspring against pertussis, but the wP-wP-aPpreg vaccination conferred offspring protection in all pregnancies at least up to 20 weeks after receiving the aPpreg-dose. In contrast, the immunity induced by aP-aP-aPpreg began to decline in births that occurred 18 weeks after receiving the aPpreg dose. For the aP-aP-aPpreg scheme, pups born from gestations furthest from aPpreg (+22 weeks) had lower PTx-specific IgG levels than those born closer to the application of the dose during pregnancy. In contrast, for pups born to wP-wP-aPpreg vaccinated mothers, the PTx-specific IgG levels were maintained over time, even for those born at the longest time studied (+22 weeks). It is noteworthy that only the pups born from mothers with aP-aP-aPpreg and receiving a neonatal dose of either aP or wP were more susceptible to infection than mice with only maternal immunity, suggesting interference with the induced immunity (p<0.05). However, it should be noted that mice with maternal immunity, whether vaccinated or not with neonatal doses, are better protected against colonization with than mice without maternal immunity but vaccinated with aP or wP.
随着许多国家引入孕妇百日咳免疫接种，人们对全细胞百日咳疫苗（wP）与无细胞疫苗（aP）对疾病控制的影响重新产生了兴趣，特别是在启动最佳方法方面。为了收集关于这一主题的证据，我们分析了 aP 或 wP 启动对孕妇接种 aP（aPpreg）的影响。采用了双母接种方案（wP-wP-aPpreg 和 aP-aP-aPpreg），并评估了母亲及其后代的免疫反应以及后代对挑战的保护作用。在第二次和第三次接种后，母亲体内均检测到百日咳毒素（PTx）特异性 IgG 反应，第三次接种后滴度更高。然而，在接受 aP-aP-aPpreg 免疫接种的母亲中，在 aPpreg 免疫接种后 22 周后，PTx-IgG 水平显著降低，但在接受 wP-wP-aPpreg 免疫接种的母亲中未观察到这种情况。aP-aP-aPpreg 方案引发了主要针对 Th2 特征的小鼠抗体反应，而 wP-wP-aPpreg 诱导了 Th1/Th2 混合特征。两种方案均能保护母亲免受百日咳感染，但 wP-wP-aPpreg 疫苗接种在接受 aPpreg 剂量后至少 20 周内，至少能保护所有妊娠的后代。相比之下，接受 aP-aP-aPpreg 免疫接种的母亲所生的后代的免疫应答开始在接受 aPpreg 剂量后 18 周时下降。对于 aP-aP-aPpreg 方案，距离 aPpreg 应用最远的妊娠（+22 周）出生的幼崽的 PTx 特异性 IgG 水平低于距离剂量应用更近的出生幼崽。相比之下，对于接受 wP-wP-aPpreg 免疫接种的母亲所生的幼崽，PTx 特异性 IgG 水平随时间保持不变，即使是在研究时间最长的幼崽（+22 周）也是如此。值得注意的是，只有来自接受 aP-aP-aPpreg 方案的母亲并接受 aP 或 wP 新生儿剂量的幼崽比只有母体免疫的幼崽更容易感染，这表明对诱导免疫的干扰（p<0.05）。然而，应当指出，无论是接受还是不接受新生儿剂量的母体免疫的小鼠，都比没有母体免疫但接种了 aP 或 wP 的小鼠更能抵抗定植。
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