美国纽约西奈山伊坎医学院Florian Krammer课题组取得一项新突破。他们提出一种基于嵌合血凝素的广泛流感病毒疫苗方法，在一项随机、安慰剂对照的I期临床试验中诱导了广泛而持久的免疫力。相关论文发表在2020年12月7日出版的《自然-医学》杂志上。
在这项完成的，实验者-双盲的、随机的、安慰剂对照的I期试验（NCT03300050）中，对健康的18至39岁美国成年人进行了嵌合血凝素疫苗的安全性和免疫原性测试。该研究旨在测试疫苗引发针对血凝素茎结构域的广泛交叉反应抗体的安全性和有效性。
参加者分为五组，分别接受减毒活疫苗、AS03灭活疫苗（n = 20）、减毒活疫苗、灭活疫苗（n = 15）、两次AS03灭活疫苗（n = 16）或安慰剂（n = 5，鼻内紧接着是肌内； n = 10，两次肌内）分别进行3个月试验。研究发现疫苗接种是安全的，并且可以针对血凝素的保守的，免疫优势的茎诱导广泛、有效、持久和功能性的免疫应答。结果表明，嵌合血凝素有可能被开发为广泛保护流感病毒的通用疫苗。
据悉，季节性流感病毒会通过抗原漂移不断变化，而大流行性流感病毒通过抗原漂移的出现是无法预测的。常规流感病毒疫苗诱导针对病毒血凝素蛋白的可变免疫优势球状头部结构域的菌株特异性中和抗体。这就需要频繁地重新配制疫苗，这会阻碍流感防范。
附：英文原文
Title: A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
Author: Raffael Nachbagauer, Jodi Feser, Abdollah Naficy, David I. Bernstein, Jeffrey Guptill, Emmanuel B. Walter, Franceso Berlanda-Scorza, Daniel Stadlbauer, Patrick C. Wilson, Teresa Aydillo, Mohammad Amin Behzadi, Disha Bhavsar, Carly Bliss, Christina Capuano, Juan Manuel Carreo, Veronika Chromikova, Carine Claeys, Lynda Coughlan, Alec W. Freyn, Christopher Gast, Andres Javier, Kaijun Jiang, Chiara Mariottini, Meagan McMahon, Monica McNeal, Alicia Solrzano, Shirin Strohmeier, Weina Sun, Marie Van der Wielen, Bruce L. Innis, Adolfo Garca-Sastre, Peter Palese, Florian Krammer
Issue&Volume: 2020-12-07
Abstract: Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18–39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed byAS03-adjuvanted inactivated vaccine (n=20), live-attenuatedfollowed byinactivated vaccine (n=15), twice AS03-adjuvanted inactivated vaccine (n=16) or placebo (n=5, intranasalfollowed byintramuscular; n=10, twice intramuscular) 3months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.
DOI: 10.1038/s41591-020-1118-7
Source: https://www.nature.com/articles/s41591-020-1118-7
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
