Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women
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DOI：
10.1001/jama.2021.7563
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发表时间：
2021-05-13
影响因子：
120.7
通讯作者：
Barouch, Dan H.
中科院分区：
文献类型：
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作者：
Collier, Ai-ris Y.;McMahan, Katherine;Barouch, Dan H.
重要的是，孕妇感染新冠肺炎的发病率和死亡率增加，但已被排除在新冠肺炎疫苗第三阶段试验之外。目的评估新冠肺炎信使核糖核酸疫苗在孕妇和哺乳期妇女中的免疫原性，包括针对新出现的SARS-CoV-2变异株的免疫原性。设计、设置和参与者一项探索性、描述性、前瞻性队列研究，纳入从2020年12月到2021年3月接种新冠肺炎疫苗的103名妇女和从2020年4月到2021年3月证实感染SARS-CoV-2的28名妇女(最后一次随访日期是2021年3月26日)。这项研究招募了30名孕妇、16名哺乳期妇女和57名未接种MERDNA或BNT162b2新冠肺炎疫苗的孕妇和22名未接种疫苗的孕妇和6名未接种疫苗的未接种SARS-CoV-2感染的孕妇和6名未接种疫苗的非妊娠妇女。用干扰素-γ酶联免疫斑点法和多参数细胞内细胞因子染色方法评价刺激性T细胞应答。对SARS-CoV-2USA-WA1/2020原始毒株以及B.1.1.7和B.1.351变异株的体液免疫和细胞免疫应答进行了检测。结果本研究纳入了103名年龄在18~45岁(66%非西班牙裔白人)的接种新冠肺炎基因疫苗的女性。在第二次接种疫苗后，报告有4名孕妇(14%；SD，6%)、7名哺乳期妇女(44%；SD，12%)和27名未怀孕妇女(52%；SD，7%)发烧。孕妇、哺乳期和非孕期妇女接种疫苗后，出现了结合、中和和功能性非中和抗体反应，以及CD4和CD8T细胞反应。在婴儿脐带血和母乳中也观察到结合抗体和中和抗体。针对SARS-CoV-2 B.1.1.7和B.1.351变异株的结合抗体和中和抗体效价降低，但T细胞对病毒变异株的反应保持不变。结论和相关性在这一方便样本的探索性分析中，孕妇接种新冠肺炎疫苗是免疫原性的，疫苗引发的抗体被输送到婴儿脐带血和母乳中。接种疫苗的孕妇和非孕妇出现了针对SARS-CoV-2变种的交叉反应抗体反应和T细胞反应。
IMPORTANCE Pregnant women are at increased risk of morbidity and mortality from COVID-19 but have been excluded from the phase 3 COVID-19 vaccine trials. Data on vaccine safety and immunogenicity in these populations are therefore limited.OBJECTIVE To evaluate the immunogenicity of COVID-19 messenger RNA (mRNA) vaccines in pregnant and lactating women, including against emerging SARS-CoV-2 variants of concern.DESIGN, SETTING, AND PARTICIPANTS An exploratory, descriptive, prospective cohort study enrolled 103 women who received a COVID-19 vaccine from December 2020 through March 2021 and 28 women who had confirmed SARS-CoV-2 infection from April 2020 through March 2021 (the last follow-up date was March 26, 2021). This study enrolled 30 pregnant, 16 lactating, and 57 neither pregnant nor lactating women who received either the mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) COVID-19 vaccines and 22 pregnant and 6 nonpregnant unvaccinated women with SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES SARS-CoV-2 receptor binding domain binding, neutralizing, and functional nonneutralizing antibody responses from pregnant, lactating, and nonpregnant women were assessed following vaccination. Spike-specific T-cell responses were evaluated using IFN-gamma enzyme-linked immunospot and multiparameter intracellular cytokine-staining assays. Humoral and cellular immune responses were determined against the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants.RESULTS This study enrolled 103 women aged 18 to 45 years (66% non-Hispanic White) who received a COVID-19 mRNA vaccine. After the second vaccine dose, fever was reported in 4 pregnant women (14%; SD, 6%), 7 lactating women (44%; SD, 12%), and 27 nonpregnant women (52%; SD, 7%). Binding, neutralizing, and functional nonneutralizing antibody responses as well as CD4 and CD8 T-cell responses were present in pregnant, lactating, and nonpregnant women following vaccination. Binding and neutralizing antibodies were also observed in infant cord blood and breast milk. Binding and neutralizing antibody titers against the SARS-CoV-2 B.1.1.7 and B.1.351 variants of concern were reduced, but T-cell responses were preserved against viral variants.CONCLUSION AND RELEVANCE In this exploratory analysis of a convenience sample, receipt of a COVID-19 mRNA vaccine was immunogenic in pregnant women, and vaccine-elicited antibodies were transported to infant cord blood and breast milk. Pregnant and nonpregnant women who were vaccinated developed cross-reactive antibody responses and T-cell responses against SARS-CoV-2 variants of concern.