美国圣路易斯华盛顿大学Michael S. Diamond课题组揭示Wuhan-1 mRNA疫苗对血清中和抗体的影响。该项研究成果于2024年5月15日在线发表在《自然》杂志上。

研究人员揭示了小鼠和人类临床试验参与者接种mRNA疫苗后血清抗体反应的特点。在小鼠中，单剂量的编码Wuhan-1的mRNA-1273疫苗临床前版本对Omicron增强剂引起的血清反应的印记最小，从而能够产生类型特异性抗体。然而，在接种了两剂mRNA-1273疫苗后再接种一剂Omicron增强剂的小鼠中观察到了印迹，而接种第二剂Omicron疫苗后印迹效应得到了缓解。在感染了SARS-CoV-2或未感染SARS-CoV-2的人类中，在接种了两剂或更多剂量的mRNA-1273原型疫苗后接种了两剂与Omicron匹配的加强剂，其刺突结合抗体和中和血清抗体与Omicron变体以及更远缘的沙巴病毒发生了交叉反应。

由于在使用Wuhan-1刺突蛋白进行预清除后，血清中针对Omicron株和其他沙巴病毒的中和反应会减弱，因此XBB.1.5增强剂在人类中诱导的抗体主要集中在前mRNA-1273主要系列所针对的保守表位上。因此，人类对以Omicron为基础的增强剂产生的抗体反应受到了历史上mRNA-1273疫苗免疫的影响，但这一结果可能是有益的，因为它促进了交叉中和抗体的扩展，从而抑制了新出现的SARS-CoV-2变体和远缘沙巴病毒的感染。

据了解，免疫印记是指先前的抗原经验会影响对随后感染或接种疫苗的反应。免疫印记对变异匹配的SARS-CoV-2疫苗增强后血清抗体反应的影响仍不确定。

附：英文原文

Title: Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines

Author: Liang, Chieh-Yu, Raju, Saravanan, Liu, Zhuoming, Li, Yuhao, Asthagiri Arunkumar, Guha, Case, James Brett, Scheaffer, Suzanne M., Zost, Seth J., Acreman, Cory M., Gagne, Matthew, Andrew, Shayne F., Carvalho dos Anjos, Deborah Carolina, Foulds, Kathryn E., McLellan, Jason S., Crowe, James E., Douek, Daniel C., Whelan, Sean P. J., Elbashir, Sayda M., Edwards, Darin K., Diamond, Michael S.

Issue&Volume: 2024-05-15

Abstract: Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here, we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2 infected or uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.

DOI: 10.1038/s41586-024-07539-1

Source: https://www.nature.com/articles/s41586-024-07539-1