接种具有抗原复杂性的血凝素混合物可提供广泛的流感疾病保护。
Vaccination with antigenically complex hemagglutinin mixtures confers broad protection from influenza disease.
机构信息
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
出版信息
Sci Transl Med. 2024 May;16(745):eadj4685. doi: 10.1126/scitranslmed.adj4685. Epub 2024 May 1.
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.
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优势但高度易变表位的反应。由于这些位点的病毒抗原漂移,疫苗需要每年更新和重新施用。为了增加流感疫苗介导的保护范围,我们开发了一种设计用于将免疫反应重新定向到蛋白质更保守结构域的重组 HA 的抗原复合物混合物。疫苗诱导的抗体不成比例地重新分布到更保守的 HA 茎部,而不会阻碍,并且在某些情况下会改善针对头部结构域的抗体反应。与传统疫苗方法相比,这些改进的反应导致对同源和异源病毒挑战的保护增加,无论是在小鼠还是雪貂中。因此,抗原复合物混合物至少可以部分克服 HA 头部结构域的抗原免疫显性,并且可能代表朝着更通用的流感疫苗迈出的一步。