Ragon Institute of MGH, MIT and Harvard, Cambridge, MA.
Division of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.
Am J Obstet Gynecol. 2022 Sep;227(3):493.e1-493.e7. doi: 10.1016/j.ajog.2022.04.009. Epub 2022 Apr 14.
SARS-CoV-2 infection is associated with enhanced disease severity in pregnant women. Despite the potential of COVID-19 vaccines to reduce severe disease, vaccine uptake remained relatively low among pregnant women. Just as coordinated messaging from the Centers for Disease Control and Prevention and leading obstetrics organizations began to increase vaccine confidence in this vulnerable group, the evolution of SARS-CoV-2 variants of concerns, including the Omicron variant, raised new concerns about vaccine efficacy because of their ability to escape vaccine-induced neutralizing antibodies. Early data point to a milder disease course following infection with the Omicron variant in vaccinated individuals. Thus, these data suggest that alternate vaccine-induced immunity beyond neutralization may continue to attenuate Omicron variant-induced disease, such as Fc-mediated antibody activity.
This study aimed to test whether vaccine-induced antibodies raised during pregnancy continue to bind to and leverage Fc receptors to protect against variants of concern including the Omicron variant.
The receptor binding domain or whole spike-specific antibody isotype binding titers and Fc gamma receptor binding directed toward variants of concern, including the Omicron variant, were analyzed in pregnant women after receiving the full dose regimen of either the Pfizer/BioNTech BNT62b2 (n=10) or Moderna mRNA-1273 (n=10) vaccination using a multiplexing Luminex assay.
Reduced isotype recognition of the Omicron receptor binding domain was observed following administration of either vaccine with relatively preserved, albeit reduced, recognition of the whole Omicron spike by immunoglobulin M and G antibodies. Despite the near complete loss of Fc receptor binding to the Omicron receptor binding domain, Fc receptor binding to the Omicron spike was more variable but largely preserved.
Reduced binding titers to the Omicron receptor binding domain aligns with the observed loss of neutralizing activity. Despite the loss of neutralization, preserved, albeit reduced, Omicron spike recognition and Fc receptor binding potentially continue to attenuate disease severity in pregnant women.
SARS-CoV-2 感染与孕妇疾病严重程度增加有关。尽管 COVID-19 疫苗有潜力降低重症疾病，但孕妇的疫苗接种率仍然相对较低。就在疾病控制与预防中心和主要产科组织的协调信息传递开始提高这个弱势群体的疫苗信心之际，包括奥密克戎变异株在内的令人关注的 SARS-CoV-2 变异株的出现引发了对疫苗效力的新担忧，因为它们能够逃避疫苗诱导的中和抗体。早期数据表明，在接种疫苗的个体中感染奥密克戎变异株后，疾病的病程较轻。因此，这些数据表明，除了中和作用之外，疫苗诱导的其他免疫反应可能继续减弱奥密克戎变异株引起的疾病，例如 Fc 介导的抗体活性。
本研究旨在测试孕妇在怀孕期间产生的疫苗诱导抗体是否继续结合并利用 Fc 受体来预防包括奥密克戎变异株在内的关注变异株。
使用多重 Luminex 分析，在 10 名接受 Pfizer/BioNTech BNT62b2（n=10）或 Moderna mRNA-1273（n=10）全剂量方案接种的孕妇中，分析了针对关注变异株（包括奥密克戎变异株）的受体结合域或全刺突特异性抗体同种型结合滴度和 Fcγ受体结合。
在接种任何一种疫苗后，均观察到奥密克戎受体结合域的同种型识别减少，而免疫球蛋白 M 和 G 抗体对全奥密克戎刺突的识别虽然减少，但仍相对保留。尽管奥密克戎受体结合域的 Fc 受体结合几乎完全丧失，但奥密克戎刺突的 Fc 受体结合更为多变，但基本保留。
对奥密克戎受体结合域的结合滴度降低与观察到的中和活性丧失一致。尽管中和作用丧失，但保留的、尽管减少的奥密克戎刺突识别和 Fc 受体结合可能继续减轻孕妇的疾病严重程度。
