Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Institute for Protein Design, University of Washington, Seattle, WA, USA.
Nature. 2021 Apr;592(7855):623-628. doi: 10.1038/s41586-021-03365-x. Epub 2021 Mar 24.
Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immunization. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens contain 20 haemagglutinin glycoprotein trimers in an ordered array, and their assembly in vitro enables the precisely controlled co-display of multiple distinct haemagglutinin proteins in defined ratios. Nanoparticle immunogens that co-display the four haemagglutinins of licensed quadrivalent influenza vaccines elicited antibody responses in several animal models against vaccine-matched strains that were equivalent to or better than commercial quadrivalent influenza vaccines, and simultaneously induced broadly protective antibody responses to heterologous viruses by targeting the subdominant yet conserved haemagglutinin stem. The combination of potent receptor-blocking and cross-reactive stem-directed antibodies induced by the nanoparticle immunogens makes them attractive candidates for a supraseasonal influenza vaccine candidate with the potential to replace conventional seasonal vaccines.
能够针对多种病毒株提供广泛且持久保护的流感疫苗将对全球健康产生重大影响，因为这将减少每年疫苗配方和免疫接种改革的需要。在这里，我们展示了经过计算设计的、由两部分组成的纳米颗粒免疫原能够诱导针对多种流感病毒的强效中和和广泛保护的抗体反应。这些纳米颗粒免疫原在有序排列中包含 20 个血凝素糖蛋白三聚体，其体外组装能够精确控制以定义的比例共同展示多种不同的血凝素蛋白。共同展示许可的四价流感疫苗的四种血凝素的纳米颗粒免疫原在几种动物模型中引发了针对疫苗匹配株的抗体反应，其效果与商业四价流感疫苗相当或更好，并且通过针对亚优势但保守的血凝素茎来同时诱导针对异源病毒的广泛保护抗体反应。纳米颗粒免疫原诱导的强效受体阻断和交叉反应性茎定向抗体的组合使它们成为具有替代传统季节性疫苗潜力的超季节性流感疫苗候选物的有吸引力的候选物。
