Page Caroline K, Shepard Justin D, Ray Sean D, Ferguson James A, Rodriguez Alesandra J, Han Julianna, Jacob Joel C, Rowe-Haas Dawne K, Akinpelu Jasmine Y, Friedman Lilach M, Hertz Tomer, Ward Andrew B, Tompkins Stephen M
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
Center for Influenza Disease and Emergence Response (CIDER), University of Georgia, Athens, GA 30602, USA.
Sci Adv. 2025 Mar 28;11(13):eadu3344. doi: 10.1126/sciadv.adu3344.
The two influenza B virus (FLUBV) lineages have continuously diverged from each other since the 1980s, with recent (post-2015) viruses exhibiting accelerated evolutionary rates. Emerging data from human studies and epidemiological models suggest that increased divergence in contemporary viruses may drive differential cross-protection, where infection with Yamagata lineage viruses provides limited immunity against Victoria lineage viruses. Here, we developed animal models to investigate the mechanisms behind asymmetric cross-protection between contemporary FLUBV lineages. Our results show that contemporary Victoria immunity provides robust cross-protection against the Yamagata lineage, whereas Yamagata immunity offers limited protection against the Victoria lineage. This differential cross-protection is driven by Victoria-elicited neuraminidase (NA)-specific antibodies, which show cross-lineage reactivity, unlike those from Yamagata infections. These findings identify a phenomenon in contemporary FLUBV that may help explain the recent disappearance of the Yamagata lineage from circulation, highlighting the crucial role of targeting NA in vaccination strategies to enhance cross-lineage FLUBV protection.
自20世纪80年代以来，两种乙型流感病毒（FLUBV）谱系不断分化，近期（2015年后）的病毒呈现出加速进化的速率。来自人体研究和流行病学模型的新数据表明，当代病毒中增加的分化可能导致不同的交叉保护，即感染山形谱系病毒对维多利亚谱系病毒的免疫力有限。在此，我们建立了动物模型来研究当代FLUBV谱系之间不对称交叉保护背后的机制。我们的结果表明，当代维多利亚谱系的免疫力对山形谱系提供了强大的交叉保护，而山形谱系的免疫力对维多利亚谱系的保护作用有限。这种不同的交叉保护是由维多利亚谱系引发的神经氨酸酶（NA）特异性抗体驱动的，这些抗体显示出跨谱系反应性，与山形谱系感染产生的抗体不同。这些发现揭示了当代FLUBV中的一种现象，这可能有助于解释山形谱系最近在流行中消失的原因，突出了在疫苗接种策略中靶向NA以增强跨谱系FLUBV保护的关键作用。
