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
Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
Department of Medicine, Division of Infectious Diseases, Stanford University, Stanford, CA, USA.
Science. 2024 Dec 20;386(6728):1389-1395. doi: 10.1126/science.adi2396. Epub 2024 Dec 19.
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.
季节性流感疫苗包含来自不同亚型的病毒株，这些病毒株是独立培养然后混合的。然而，大多数个体对其中一种病毒株表现出更强的反应，因此容易受到其他病毒株的感染。通过研究同卵双胞胎队列，我们发现虽然先前接触是一个因素，但宿主基因是流感病毒株亚型偏向的更强驱动因素。我们发现，来自不同病毒株的异源血凝素（HA）的共价偶联在动物模型和人扁桃体类器官系统中可以在很大程度上消除亚型偏向。我们提出，异源抗原的偶联通过扩大T细胞辅助来改善针对流感病毒株的抗体反应，并且我们发现使用这种方法可显著改善对禽流感HA的抗体反应。
