Coupling antigens from multiple subtypes of influenza can broaden antibody and T cell responses

• 成果类型: Article
• 署名作者: Mallajosyula, Vamsee; Chakraborty, Saborni; Sola, Elsa; Fong, Ryan Furuichi; Shankar, Vishnu; Gao, Fei; Burrell, Allison R.; Gupta, Neha; Wagar, Lisa E.; Mischel, Paul S.; Capasso, Robson; Staat, Mary A.; Chien, Yueh-Hsiu; Dekker, Cornelia L.; Wang, Taia T.; Davis, Mark M.
• 署名单位: Stanford University; Stanford University; Stanford University; University System of Ohio; University of Cincinnati; Cincinnati Children's Hospital Medical Center; University of California System; University of California Irvine; Stanford University; Stanford University; Stanford University; Stanford University; Stanford University; Howard Hughes Medical Institute; Stanford University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11585
• DOI: 10.1126/science.adi2396
• 发表日期: 2024-12-20
• 页码: 1389-1395
• 关键词: virus infection; vaccine; HISTORY; help; driven; sin

摘要

The seasonal influenza vaccine contains strains of viruses from distinct subtypes that are grown independently and then combined. However, most individuals exhibit a more robust response to one of these strains and thus are vulnerable to infection by others. By studying a monozygotic twin cohort, we found that although prior exposure is a factor, host genetics are a stronger driver of subtype bias to influenza viral strains. We found that covalent coupling of heterologous hemagglutinin (HA) from different viral strains could largely eliminate subtype bias in an animal model and in a human tonsil organoid system. We proposed that coupling of heterologous antigens improves antibody responses across influenza strains by broadening T cell help, and we found that using this approach substantially improved the antibody response to avian influenza HA.