Current seasonal influenza virus vaccines induce responses primarily against immunodominant but highly plastic epitopes in the globular head of the hemagglutinin (HA) glycoprotein. Because of viral antigenic drift at these sites, vaccines need to be updated and readministered annually. To increase the breadth of influenza vaccine–mediated protection, we developed an antigenically complex mixture of recombinant HAs designed to redirect immune responses to more conserved domains of the protein. Vaccine-induced antibodies were disproportionally redistributed to the more conserved stalk of the HA without hindering, and in some cases improving, antibody responses against the head domain. These improved responses led to increased protection against homologous and heterologous viral challenges in both mice and ferrets compared with conventional vaccine approaches. Thus, antigenically complex protein mixtures can at least partially overcome HA head domain antigenic immunodominance and may represent a step toward a more universal influenza vaccine.

中文翻译：

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使用抗原复合血凝素混合物进行疫苗接种可提供对流感疾病的广泛保护


目前的季节性流感病毒疫苗主要诱导针对血凝素 (HA) 糖蛋白球状头部中免疫显性但高度可塑性的表位的反应。由于这些部位的病毒抗原漂移，疫苗需要每年更新和重新接种。为了扩大流感疫苗介导的保护范围，我们开发了一种重组 HA 的抗原性复杂混合物，旨在将免疫反应重定向到更保守的蛋白质结构域。疫苗诱导的抗体不成比例地重新分配到 HA 更保守的茎部，而不会阻碍（在某些情况下还改善）针对头部结构域的抗体反应。与传统疫苗方法相比，这些改善的反应导致小鼠和雪貂对同源和异源病毒攻击的保护增强。因此，抗原复合蛋白混合物可以至少部分克服HA头结构域抗原免疫优势，并可能代表朝着更通用的流感疫苗迈出的一步。