Influenza vaccine based on AS03-adjuvanted chimeric HA induces long-lived stalk-specific plasma cells in bone marrow and lymph nodes of nonhuman primates.

IF 27.6 1区医学 Q1 IMMUNOLOGY

Nature Immunology Pub Date : 2025-10-15 DOI:10.1038/s41590-025-02309-1

Akil Akhtar,Tiffany M Styles,Chunyang Gu,André Nicolás León,Gregory K Tharp,Kasey Stokdyk,Anass Abbad,Cora Hirst,Shirin Strohmeier,Gabriele Neumann,Sara T Richey,James A Ferguson,Uchurappa Mala,Hasan Ahmed,Julianna Han,Juan Manuel Carreño,Carl W Davis,Rustom Antia,Peter Palese,Andrew B Ward,Yoshihiro Kawaoka,Florian Krammer,Rafi Ahmed,Rama R Amara

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Abstract

Current influenza vaccines face challenges due to antigenic evolution of the circulating virus and waning immunity in humans. Here we investigated the durability of humoral immunity induced by an influenza vaccine based on AS03-adjuvanted chimeric hemagglutinin (cHA) in nonhuman primates (NHPs). Two groups of NHPs received two doses of a seasonal quadrivalent influenza vaccine, followed by sequential immunization with split virus cHA vaccines cH8/1N1, and cH5/1N1. One group received cHA immunizations with AS03 adjuvant. We monitored serum antibodies and long-lived plasma cells in bone marrow for nearly 2 years after the final vaccination. cHA vaccines induced stalk-specific antibody responses. The addition of AS03 enhanced both the magnitude and durability of humoral immunity by establishing long-lived plasma cells in the bone marrow and lymph nodes for nearly 2 years. Passive transfer of NHP serum provided protection against challenge with heterologous influenza A virus strains in mice. This study highlights the potential of the AS03-adjuvanted chimeric HA vaccine strategy to provide durable and broadly protective humoral immunity.

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基于as03佐剂嵌合HA的流感疫苗在非人灵长类动物的骨髓和淋巴结中诱导了长寿命的茎特异性浆细胞。

由于流行病毒的抗原进化和人类免疫力下降，目前的流感疫苗面临挑战。本文研究了基于as03佐剂嵌合血凝素（cHA）的流感疫苗在非人灵长类动物（NHPs）中诱导的体液免疫的持久性。两组NHPs接种了两剂季节性四价流感疫苗，随后依次接种cHA分裂病毒疫苗cH8/1N1和cH5/1N1。一组用AS03佐剂进行cHA免疫。在最后一次接种疫苗后，我们监测了近2年的血清抗体和骨髓中的长寿命浆细胞。cHA疫苗诱导茎特异性抗体反应。AS03的加入通过在骨髓和淋巴结中建立寿命近2年的长浆细胞，增强了体液免疫的强度和持久性。NHP血清的被动转移对小鼠抗异源甲型流感病毒株的攻击具有保护作用。这项研究强调了as03佐剂嵌合HA疫苗策略在提供持久和广泛保护性体液免疫方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Immunology 医学-免疫学

CiteScore

40.00

自引率

2.30%

发文量

248

审稿时长

4-8 weeks

期刊介绍： Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.