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基于 mRNA 和腺病毒的 COVID-19 疫苗诱导的 SARS-CoV-2 刺突特异性人乳抗体的比较特征。

Comparative Profiles of SARS-CoV-2 Spike-Specific Human Milk Antibodies Elicited by mRNA- and Adenovirus-Based COVID-19 Vaccines.

机构信息

Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Division of Cancer, Department of Surgery and Cancer, Imperial College London, London, United Kingdom.

出版信息

Breastfeed Med. 2022 Aug;17(8):638-646. doi: 10.1089/bfm.2022.0019. Epub 2022 Jun 8.

DOI:10.1089/bfm.2022.0019
PMID:35675683
Abstract

Numerous COVID-19 vaccines are authorized globally. To date, ∼71% of doses comprise the Pfizer/BioNTech vaccine, and ∼17% the Moderna/NIH vaccine, both of which are messenger RNA (mRNA) based. The chimpanzee Ad-based Oxford/AstraZeneca (AZ) vaccine comprises ∼9%, while the Johnson & Johnson/Janssen (J&J) human adenovirus (Ad26) vaccine ranks fourth at ∼2%. No COVID-19 vaccine is yet available for children 0-4. One method to protect this population may be passive immunization through antibodies (Abs) provided in the milk of a lactating vaccinated person. Our early work and other reports have demonstrated that unlike the post-SARS-CoV-2 infection milk Ab profile, which is rich in specific secretory (s)IgA, the vaccine response is highly IgG dominant. In this report, we present a comparative assessment of the milk Ab response elicited by Pfizer, Moderna, J&J, and AZ vaccines. This analysis revealed 86-100% of mRNA vaccine recipient milk exhibited Spike-specific IgG endpoint titers, which were 12- to 28-fold higher than those measured for Ad vaccine recipient milk. Ad-based vaccines elicited Spike-specific milk IgG in only 33-38% of recipients. Specific IgA was measured in 52-71% of mRNA vaccine recipient milk and 17-23% of Ad vaccine recipient milk. J&J recipient milk exhibited significantly lower IgA than Moderna recipients, and AZ recipients exhibited significantly lower IgA titers than Moderna and Pfizer. Less than 50% of milk of any group exhibited specific secretory Ab, with Moderna recipient IgA titers measuring significantly higher than AZ. Moderna appeared to most frequently elicit greater than twofold increases in specific secretory Ab titer relative to prevaccine sample. These data indicate that current Ad-based COVID-19 vaccines poorly elicit Spike-specific Ab in milk compared to mRNA-based vaccines, and that mRNA vaccines are preferred for immunizing the lactating population. This study highlights the need to design vaccines better aimed at eliciting an optimal milk Ab response.

摘要

全球有多种 COVID-19 疫苗获得授权。迄今为止,约 71%的剂量由辉瑞/生物技术公司疫苗组成,约 17%的剂量由 Moderna/NIH 疫苗组成,这两种疫苗都是基于信使 RNA (mRNA) 的。基于黑猩猩腺病毒的牛津/阿斯利康 (AZ) 疫苗占约 9%,而强生/杨森 (J&J) 腺病毒 26 型 (Ad26) 疫苗排名第四,占约 2%。目前还没有针对 0-4 岁儿童的 COVID-19 疫苗。保护这一人群的一种方法可能是通过哺乳期接种者的乳汁中提供的抗体 (Abs) 进行被动免疫。我们的早期工作和其他报告表明,与感染 SARS-CoV-2 后的乳汁 Ab 谱不同,后者富含特异性分泌 (s)IgA,疫苗反应高度 IgG 占主导地位。在本报告中,我们对辉瑞、Moderna、J&J 和 AZ 疫苗引起的乳汁 Ab 反应进行了比较评估。该分析显示,86-100%的 mRNA 疫苗接种者的乳汁中均表现出 Spike 特异性 IgG 终点滴度,比 Ad 疫苗接种者的乳汁高 12-28 倍。Ad 疫苗仅在 33-38%的接种者中引起 Spike 特异性乳汁 IgG。在 52-71%的 mRNA 疫苗接种者的乳汁和 17-23%的 Ad 疫苗接种者的乳汁中检测到特异性 IgA。J&J 疫苗接种者的乳汁 IgA 显著低于 Moderna 疫苗接种者,而 AZ 疫苗接种者的 IgA 滴度显著低于 Moderna 和辉瑞。不到 50%的乳汁具有特异性分泌 Ab,其中 Moderna 疫苗接种者的 IgA 滴度显著高于 AZ。Moderna 似乎最常引起特异性分泌 Ab 滴度比预疫苗样本增加两倍以上。这些数据表明,与基于 mRNA 的疫苗相比,目前基于 Ad 的 COVID-19 疫苗在乳汁中不能很好地引起 Spike 特异性 Ab,而 mRNA 疫苗更适合用于免疫哺乳期人群。本研究强调需要设计更好的疫苗来引起最佳的乳汁 Ab 反应。

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