Robinson-McCarthy Lindsey R, Simmons Holly C, Graber Aaron L, Marble Carly N, Graudin Grace W, McCarthy Kevin R
Center for Vaccine Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Virol. 2025 Sep 23;99(9):e0062125. doi: 10.1128/jvi.00621-25. Epub 2025 Aug 25.
An unprecedented outbreak of a highly pathogenic avian influenza virus, H5 clade 2.3.4.4b, was reported in U.S. dairy cattle during the spring of 2024. It has now spread to hundreds of herds across multiple states. In humans, antibodies to the hemagglutinin (HA) protein confer the strongest protection against infection. Human herd immunity limits viral spread but also drives the emergence of antigenic variants that escape dominant antibody responses. We used store-bought milk to profile the collective H5N1 antibody response of dairy cattle herds. We detected HA binding antibodies in specific samples from states with recent/ongoing outbreaks. These antibodies present in milk neutralized replicating virus expressing dairy cattle HA and neuraminidase (NA). Despite originating from independent vendors, dairies/plants, geographic regions, and time, antibodies present in these samples are remarkably similar in activity and HA binding specificity. The dominant antibody response was clade 2.3.4.4b HA specific, followed by cross-reactivity with other H5s. Whether the uniformity of the response is a pathway to achieve herd immunity or an avenue for antigenic variants to rapidly escape remains to be seen.IMPORTANCEEstablishing human herd immunity ends pandemics. For influenza viruses, this immunity drives continued antigenic evolution that enables viruses to infect once-immune individuals. An outbreak of highly pathogenic avian influenza virus was detected in dairy cattle in 2024 and has spread rapidly across herds and states. We report approaches to assess dairy cattle herd immunity using store-bought milk samples. Across samples separated by geography and time, we find dairy cattle mount a strikingly similar antibody response that is strongest to the dairy cattle virus. Benchmarking immunity at this phase of the outbreak is important to understand either eradication or the emergence of antigenic variants that enable reinfection.
2024年春季，美国奶牛群中报告了一种高致病性禽流感病毒H5进化枝2.3.4.4b前所未有的爆发情况。目前，它已传播到多个州的数百个牛群。在人类中，针对血凝素（HA）蛋白的抗体提供了针对感染的最强保护。人群免疫限制了病毒传播，但也促使逃避主要抗体反应的抗原变体出现。我们使用市售牛奶来分析奶牛群对H5N1的集体抗体反应。我们在近期/正在爆发疫情的州的特定样本中检测到了HA结合抗体。这些存在于牛奶中的抗体中和了表达奶牛HA和神经氨酸酶（NA）的复制病毒。尽管这些样本来自独立供应商、乳品厂/加工厂、地理区域和时间，但其中存在的抗体在活性和HA结合特异性方面非常相似。主要的抗体反应是针对2.3.4.4b进化枝HA特异性的，其次是与其他H5的交叉反应性。这种反应的一致性是实现群体免疫的途径还是抗原变体迅速逃逸的途径，还有待观察。
重要性
建立人群免疫可终结大流行。对于流感病毒而言，这种免疫会推动持续的抗原进化，使病毒能够感染曾经免疫的个体。2024年在奶牛中检测到高致病性禽流感病毒爆发，且已迅速在牛群和各州传播。我们报告了使用市售牛奶样本评估奶牛群免疫的方法。在按地理和时间分隔的样本中，我们发现奶牛产生了惊人相似的抗体反应，对奶牛病毒的反应最强。在疫情的这个阶段对免疫进行基准评估，对于了解根除情况或能够导致再次感染的抗原变体的出现很重要。
