Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892;
Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, 40530 Gothenburg, Sweden.
Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13474-13479. doi: 10.1073/pnas.1816300116. Epub 2019 Jun 18.
A major obstacle to vaccination against antigenically variable viruses is skewing of antibody responses to variable immunodominant epitopes. For influenza virus hemagglutinin (HA), the immunodominance of the variable head impairs responses to the highly conserved stem. Here, we show that head immunodominance depends on the physical attachment of head to stem. Stem immunogenicity is enhanced by immunizing with stem-only constructs or by increasing local HA concentration in the draining lymph node. Surprisingly, coimmunization of full-length HA and stem alters stem-antibody class switching. Our findings delineate strategies for overcoming immunodominance, with important implications for human vaccination.
针对抗原变异病毒的疫苗接种主要存在一个障碍，即抗体反应会偏向于可变免疫显性表位。对于流感病毒血凝素（HA），可变头部的免疫显性会损害对高度保守茎部的反应。在这里，我们表明头部的免疫显性取决于头部与茎部的物理连接。通过仅用茎部构建体免疫或增加引流淋巴结中 HA 的局部浓度，可增强茎部的免疫原性。令人惊讶的是，全长 HA 和茎部的共同免疫会改变茎部抗体的类别转换。我们的发现描绘了克服免疫显性的策略，这对人类疫苗接种具有重要意义。
