Kikawa Caroline, Loes Andrea N, Huddleston John, Figgins Marlin D, Steinberg Philippa, Griffiths Tachianna, Drapeau Elizabeth M, Peck Heidi, Barr Ian G, Englund Janet A, Hensley Scott E, Bedford Trevor, Bloom Jesse D
Division of Basic Sciences and Computational Biology Program, Fred Hutch Cancer Center, Seattle, WA.
Department of Genome Sciences, University of Washington, Seattle, WA.
bioRxiv. 2025 Mar 12:2025.03.04.641544. doi: 10.1101/2025.03.04.641544.
Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera, measuring ~10,000 total titers. There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution. Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influenza.
人流感病毒会在其血凝素（HA）蛋白中迅速获得突变，从而削弱先前接触产生的抗体的中和作用。在此，我们使用基于测序的检测方法，针对大量儿童和成人血清，测量了78种近期H3N2 HA毒株的中和滴度，总共测量了约10000个滴度。在不同年龄组内和不同年龄组之间，针对不同病毒株的滴度存在显著的个体差异。2023年H3N2毒株在人群中的生长速率与针对每种毒株的低滴度血清比例高度相关。值得注意的是，毒株生长速率与针对人血清池的中和滴度相关性较低，这表明群体异质性在塑造病毒进化过程中的重要性。总体而言，这些结果表明，对人血清针对多种不同病毒株进行高通量中和测量有助于解释人流感的进化。
