朝着一种综合性流感疫苗迈进: 新的动物模型研究可能开启制造一种能抵御范围广泛的病毒株的流感疫苗之门，人们因此可在每年使用该种疫苗。 Chih-Jen Wei及其同僚报告说，事先用来自流感病毒的DNA来刺激免疫系统（在用一种季节性流感疫苗来增强免疫系统之前）可在小鼠、雪貂和非人的灵长类动物中产生能中和广范围H1N1病毒的抗体。 目前，季节性流感疫苗可诱导产生以病毒血凝素（HA）蛋白为标靶的抗体，但这种蛋白会快速突变，令病毒对该种疫苗产生抵抗力。 HA蛋白的某些区域较为稳定，因此研究人员更愿意设计一种可诱发以这些区域为标靶之抗体的疫苗，并进而能够保护机体抵抗范围广泛的病毒株。 Wei及其同僚如今显示，一种“预刺激-增强”组合疫苗可在动物模型中提供对机体的保护。 该“预刺激引物”是由编码流感HA的DNA所组成的，而该“增强剂”则是一种常规的季节性流感疫苗。 这种组合疫苗可中和取自小鼠、雪貂和非人类的灵长目动物血清样本中的病毒，它还能在小鼠和雪貂中保护其机体不会被另外一种不同的流感病毒株感染。 有必要开展进一步的研究以测定这种疫苗策略或类似的疫苗策略在人体中应用时会有多理想。 文章的作者指出，在人体中预先存在的流感免疫力会影响疫苗的功效， 但在这一例子中，该疫苗仍然可用于那些还没有预先存在免疫力的幼童和婴儿。
Article #26: "Induction of Broadly Neutralizing H1N1 Influenza Antibodies by Vaccination," by C.-J. Wei; J.C. Boyington; P.M. McTamney; W.-P. Kong; L. Xu; S. Rao; Z.-Y. Yang; G.J. Nabel at National Institute of Allergy and Infectious Diseases, National Institutes of Health in Bethesda, MD; M.B. Pearce; T.M. Tumpey at Centers for Disease Control and Prevention in Atlanta, GA; H. Andersen at BIOQUAL, Inc. in Rockville, MD.
联系人: Gary J. Nabel，+1-301-496-1852 (电话), 或 gnabel@nih.gov (电子邮件)。NIH/NIAID 新闻办公室， +1-301-402-1663 (电话)。
Published Online July 15, 2010
Science DOI: 10.1126/science.1192517
Reports
Induction of Broadly Neutralizing H1N1 Influenza Antibodies by Vaccination
Chih-Jen Wei,1 Jeffrey C. Boyington,1 Patrick M. McTamney,1 Wing-Pui Kong,1 Melissa B. Pearce,2 Ling Xu,1 Hanne Andersen,3 Srinivas Rao,1 Terrence M. Tumpey,2 Zhi-Yong Yang,1 Gary J. Nabel1,*
The rapid dissemination of the 2009 pandemic influenza virus underscores the need for universal influenza vaccines that elicit protective immunity to diverse viral strains. Here, we show that vaccination with plasmid DNA encoding H1N1 influenza hemagglutinin (HA) and boosting with seasonal vaccine or replication-defective adenovirus 5 (rAd5) vector encoding HA stimulated the production of broadly neutralizing influenza antibodies. This prime-boost combination increased neutralization of diverse H1N1 strains from 1934 to 2007 compared to either component alone and conferred protection against divergent H1N1 viruses in mice and ferrets. These antibodies were directed to the conserved stem region of HA and were also elicited in nonhuman primates. Cross-neutralization of H1N1 subtypes elicited by this approach provides a basis for development of a universal influenza vaccine for humans.
