BACKGROUND Respiratory Syncytial Virus (RSV) is associated with significant neonatal and infant morbidity and mortality. Maternal bivalent RSVpreF RSV vaccination to protect neonates and infants was approved in September 2023 for administration between 32+0 and 36+6 weeks to protect neonates and infants. This approved timeframe is narrower than the 24-36 week window evaluated in the clinical trial, due to the possible association between preterm birth and vaccine administration. Currently, data are lacking on how maternal vaccine timing within the approved window affects the transfer of antibodies from mother to fetus, critical information that could influence clinical practice. OBJECTIVES We sought to examine how gestational age at vaccination and time elapsed from maternal RSV vaccination to delivery impacted transfer of maternal antibodies measured in the umbilical cord at delivery and in peripheral blood of 2-month infants. We also examined differences in maternal and cord RSV antibody levels achieved by vaccination versus natural RSV infection. STUDY DESIGN A prospective cohort study was conducted at two academic medical centers between September 20, 2023 and March 21, 2024, enrolling 124 individuals who received the RSV vaccine during pregnancy. Infant capillary blood was collected at 2 months of age from 29 of the infants. Maternal and cord IgG levels achieved by RSV vaccination were compared to those associated with maternal natural RSV infection, using banked blood from 20 maternal:cord dyads collected prior to the availability of the maternal RSV vaccine. Levels of IgG against RSV strain A2 and B fusion (F) and attachment (G) proteins and against pertussis toxin (as a comparator antigen from a vaccine routinely administered earlier in pregnancy) were measured using a Binding Antibody Multiplex Assay. Differences in titers between vaccination and natural infection were examined using Wilcoxon rank sum test. Differences in cord:maternal transfer ratios and 2-month infant antibody levels by timing of maternal vaccination were evaluated by Kruskal-Wallis testing. RESULTS Maternal RSV vaccination resulted in significantly higher maternal and cord anti-RSV F antibody levels than natural infection (5.72 vs 4.82 log10MFI, p < 0.0001 maternal; 5.81 vs 5.03 log10MFI, p < 0.0001 cord). Maternal vaccination 2-3 weeks and 3-4 weeks prior to delivery was associated with significantly lower cord:maternal transfer ratios than were observed when vaccination occurred > 5 weeks prior to delivery (p = 0.03 for 2-3 weeks, p = 0.007 for 3-4 weeks), and significantly lower transfer ratios than observed for pertussis vaccination administered prior to 30 weeks' gestation (p = 0.008 for 2-3 weeks, p = 0.03 for 3-4 weeks, similar at > 4 weeks). CONCLUSION (s): Vaccine administration earlier in the approved 32-36 week window (at least 5 weeks prior to delivery) results in the highest transplacental transfer of maternal antibodies to the neonate. These results should inform the counseling of pregnant individuals on optimal vaccination timing.

中文翻译：

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提高胎盘抗体转移效率，延长母体 RSV 疫苗接种和出生之间的间隔。


背景 呼吸道合胞病毒 （RSV） 与显着的新生儿和婴儿发病率和死亡率有关。2023 年 9 月，用于保护新生儿和婴儿的母体二价 RSVpreF RSV 疫苗接种被批准在 32+0 至 36+6 周之间接种，以保护新生儿和婴儿。由于早产与疫苗接种之间可能存在关联，该批准的时间范围比临床试验中评估的 24-36 周窗口窄。目前，缺乏关于在批准窗口内母体接种疫苗的时间如何影响抗体从母亲到胎儿的转移的数据，这些信息可能会影响临床实践。目的 我们试图检查接种疫苗时的胎龄和从母体 RSV 疫苗接种到分娩所经过的时间如何影响分娩时脐带和 2 个月婴儿外周血中测量的母体抗体的转移。我们还检查了疫苗接种与自然 RSV 感染所达到的母体和脐带 RSV 抗体水平的差异。研究设计 2023 年 9 月 20 日至 2024 年 3 月 21 日期间，在两个学术医疗中心进行了一项前瞻性队列研究，招募了 124 名在怀孕期间接种 RSV 疫苗的个体。从 29 名婴儿的 2 个月大时收集婴儿毛细血管血。使用在母体 RSV 疫苗可用之前收集的 20 个母体：脐带二元组的库存血液，将 RSV 疫苗接种达到的母体和脐带 IgG 水平与母体自然 RSV 感染相关的水平进行比较。 使用结合抗体多重测定法测量针对 RSV 菌株 A2 和 B 融合 （F） 和附着 （G） 蛋白以及百日咳毒素（作为怀孕早期常规接种的疫苗的对照抗原）的 IgG 水平。使用 Wilcoxon 秩和检验检查疫苗接种和自然感染之间滴度的差异。通过 Kruskal-Wallis 测试评估母体疫苗接种时间的脐带：母体转移比率和 2 个月婴儿抗体水平的差异。结果 母体 RSV 疫苗接种导致母体和脐带抗 RSV F 抗体水平显著高于自然感染（5.72 vs 4.82 log10MFI，p < 0.0001 母体;5.81 vs 5.03 log10MFI，p < 0.0001 脐带）。分娩前 2-3 周和 3-4 周的母体疫苗接种与观察到的脐带：母体转移比率显著低于分娩前 5 周接种疫苗时观察到的 > 相关（p = 0.03，p = 0.007 3-4 周），并且转移比率显著低于妊娠 30 周前接种百日咳疫苗时观察到的转移比率（p = 0.008 2-3 周， p = 0.03 持续 3-4 周，与 > 相似 4 周）。结论： 在批准的 32-36 周窗口早期 （至少在分娩前 5 周） 接种疫苗导致母体抗体经胎盘向新生儿的转移最高。这些结果应为孕妇最佳疫苗接种时间的咨询提供信息。