Ort Jordan T, Leonard Ashley Sobel, Li Shuk Hang, Atkinson Reilly K, Mendoza Lydia M, Vieira Marcos Costa, Gang Sydney, Cobey Sarah, Hensley Scott E
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
medRxiv. 2025 Sep 4:2025.09.02.25334929. doi: 10.1101/2025.09.02.25334929.
H5N1 highly pathogenic avian influenza viruses have spread globally and pose a risk for a human pandemic. Prior studies suggest that early life exposures to group 1 influenza viruses (H1N1 and H2N2) prime antibodies that cross-react to the hemagglutinin of H5N1, which is also a group 1 virus. Less is known about how immune history affects antibody responses against the neuraminidase (NA) of H5N1 viruses. Here, we measured NA inhibition antibodies against multiple H5N1 viruses using sera from 155 individuals born between 1927 and 2016. We found that individuals primed in childhood with H1N1 viruses were more likely to possess higher levels of antibodies that cross-react with the NA of H5N1 viruses compared to individuals primed in childhood with H2N2 or H3N2 viruses. While young children rarely possessed cross-reactive NA antibodies, we found that childhood infections with contemporary H1N1, but not H3N2, viruses can elicit them. These data suggest that immune history greatly impacts the generation of cross-reactive NA antibodies that can inhibit H5N1 viruses.
H5N1高致病性禽流感病毒已在全球传播，对人类大流行构成风险。先前的研究表明，早年接触1型流感病毒（H1N1和H2N2）会引发与H5N1血凝素发生交叉反应的抗体，H5N1也是1型病毒。关于免疫史如何影响针对H5N1病毒神经氨酸酶（NA）的抗体反应，人们了解较少。在此，我们使用1927年至2016年间出生的155名个体的血清，测量了针对多种H5N1病毒的NA抑制抗体。我们发现，与童年时期接触H2N2或H3N2病毒的个体相比，童年时期接触H1N1病毒的个体更有可能拥有与H5N1病毒NA发生交叉反应的高水平抗体。虽然幼儿很少拥有交叉反应性NA抗体，但我们发现，童年时期感染当代H1N1病毒而非H3N2病毒可引发此类抗体。这些数据表明，免疫史极大地影响了能够抑制H5N1病毒的交叉反应性NA抗体的产生。
