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孕期接种新冠病毒加强针可增强母体的结合抗体和中和抗体反应以及抗体经胎盘向新生儿的转移(DMID 21-0004)。

COVID-19 booster vaccination during pregnancy enhances maternal binding and neutralizing antibody responses and transplacental antibody transfer to the newborn (DMID 21-0004).

作者信息

Munoz Flor M, Posavad Christine M, Richardson Barbra A, Badell Martina L, Bunge Katherine, Mulligan Mark J, Parameswaran Lalitha, Kelly Clifton, Olsen-Chen Courtney, Novak Richard M, Brady Rebecca C, Pasetti Marcela, DeFranco Emily, Gerber Jeffrey S, Shriver Mallory, Suthar Mehul S, Moore Kathryn, Coler Rhea, Berube Bryan, Kim So Hee, Piper Jeanna M, Miller Ashley, Cardemil Cristina, Neuzil Kathleen M, Beigi Richard

出版信息

medRxiv. 2022 Jun 13:2022.06.13.22276354. doi: 10.1101/2022.06.13.22276354.

Abstract

IMPORTANCE

COVID-19 vaccination is recommended during pregnancy for the protection of the mother. Little is known about the immune response to booster vaccinations during pregnancy.

OBJECTIVE

To measure immune responses to COVID-19 primary and booster mRNA vaccination during pregnancy and transplacental antibody transfer to the newborn.

DESIGN

Prospective cohort study of pregnant participants enrolled from July 2021 to January 2022, with follow up through and up to 12 months after delivery.

SETTING

Multicenter study conducted at 9 academic sites.

PARTICIPANTS

Pregnant participants who received COVID-19 vaccination during pregnancy and their newborns.

EXPOSURES

Primary or booster COVID-19 mRNA vaccination during pregnancy.

MAIN OUTCOMES AND MEASURES

SARS-CoV-2 binding and neutralizing antibody (nAb) titers after primary or booster COVID-19 mRNA vaccination during pregnancy and antibody transfer to the newborn. Immune responses were compared between primary and booster vaccine recipients in maternal sera at delivery and in cord blood, after adjusting for days since last vaccination.

RESULTS

In this interim analysis, 167 participants received a primary 2-dose series and 73 received a booster dose of mRNA vaccine during pregnancy. Booster vaccination resulted in significantly higher binding and nAb titers, including to the Omicron BA.1 variant, in maternal serum at delivery and cord blood compared to a primary 2-dose series (range 0.55 to 0.88 log higher, p<0.0001 for all comparisons). Although levels were significantly lower than to the prototypical D614G variant, nAb to Omicron were present at delivery in 9% (GMT ID50 12.7) of Pfizer and 22% (GMT ID50 14.7) of Moderna recipients, and in 73% (GMT ID50 60.2) of boosted participants (p<0.0001). Transplacental antibody transfer was efficient regardless of vaccination regimen (median transfer ratio range: 1.55-1.77 for binding IgG and 1.00-1.78 for nAb).

CONCLUSIONS AND RELEVANCE

COVID-19 mRNA vaccination during pregnancy elicited robust immune responses in mothers and efficient transplacental antibody transfer to the newborn. A booster dose during pregnancy significantly increased maternal and cord blood antibody levels, including against Omicron.Findings support continued use of COVID-19 vaccines during pregnancy, including booster doses.

TRIAL REGISTRATION

clinical trials.gov; Registration Number: NCT05031468 ; https://clinicaltrials.gov/ct2/show/NCT05031468.

KEY POINTS

What is the immune response after COVID-19 booster vaccination during pregnancy and how does receipt of a booster dose impact transplacental antibody transfer to the newborn? Receipt of COVID-19 mRNA vaccines during pregnancy elicited robust binding and neutralizing antibody responses in the mother and in the newborn. Booster vaccination during pregnancy elicited significantly higher antibody levels in mothers at delivery and cord blood than 2-dose vaccination, including against the Omicron BA.1 variant. COVID-19 vaccines, especially booster doses, should continue to be strongly recommended during pregnancy.

摘要

重要性

推荐在孕期接种新冠病毒疫苗以保护母亲。关于孕期加强疫苗接种后的免疫反应知之甚少。

目的

测量孕期新冠病毒初次和加强mRNA疫苗接种后的免疫反应以及经胎盘向新生儿的抗体转移情况。

设计

对2021年7月至2022年1月登记入组的孕妇进行前瞻性队列研究,并在分娩后随访长达12个月。

地点

在9个学术地点进行的多中心研究。

参与者

孕期接种新冠病毒疫苗的孕妇及其新生儿。

暴露因素

孕期进行新冠病毒初次或加强mRNA疫苗接种。

主要结局和测量指标

孕期新冠病毒初次或加强mRNA疫苗接种后严重急性呼吸综合征冠状病毒2(SARS-CoV-2)结合抗体和中和抗体(nAb)滴度以及向新生儿的抗体转移情况。在调整末次接种后的天数后,比较分娩时母亲血清和脐带血中初次和加强疫苗接种者的免疫反应。

结果

在这项中期分析中,167名参与者在孕期接受了2剂次的初次疫苗接种,73名接受了加强剂量的mRNA疫苗接种。与2剂次的初次疫苗接种系列相比,加强疫苗接种导致分娩时母亲血清和脐带血中的结合抗体和nAb滴度显著更高,包括针对奥密克戎BA.1变体(所有比较的差异范围为0.55至0.88对数,p<0.0001)。尽管水平显著低于针对原型D614G变体的水平,但在辉瑞疫苗接种者中,9%(几何平均滴度[GMT] ID50为12.7)、莫德纳疫苗接种者中22%(GMT ID50为14.7)以及加强接种参与者中73%(GMT ID50为60.2)在分娩时存在针对奥密克戎的nAb(p<0.0001)。无论接种方案如何,经胎盘抗体转移都是有效的(结合IgG的中位转移率范围为1.55 - 1.77,nAb为1.00 - 1.78)。

结论和相关性

孕期接种新冠病毒mRNA疫苗在母亲中引发了强烈的免疫反应,并有效地经胎盘向新生儿转移抗体。孕期接种加强剂量显著提高了母亲和脐带血中的抗体水平,包括针对奥密克戎的抗体。研究结果支持在孕期继续使用新冠病毒疫苗,包括加强剂量。

试验注册

clinicaltrials.gov;注册号:NCT05031468;https://clinicaltrials.gov/ct2/show/NCT05031468。

关键点

孕期接种新冠病毒加强疫苗后的免疫反应如何,接种加强剂量对经胎盘向新生儿的抗体转移有何影响?孕期接种新冠病毒mRNA疫苗在母亲和新生儿中引发了强烈的结合抗体和中和抗体反应。孕期接种加强疫苗导致分娩时母亲和脐带血中的抗体水平显著高于2剂次接种,包括针对奥密克戎BA.1变体。在孕期应继续强烈推荐接种新冠病毒疫苗,尤其是加强剂量。

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