带有趋化因子佐剂CTACK的季节性H1流感血凝素纳米颗粒疫苗的DNA共递送在体内诱导了强有力的异源保护免疫原性

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-05-20 DOI:10.1016/j.vaccine.2025.127231

Kevin Liaw , Kylie M. Konrath , Abigail R. Trachtman , Nicholas J. Tursi , Ebony N. Gary , Cory Livingston , Kaitlyn Flowers , Jacqueline D. Chu , Casey E. Hojecki , Niklas Laenger , Madison E. McCanna , Colby J. Agostino , Neethu Chokkalingam , Kelly Bayruns , Sinja Kriete , Amber Kim , Joyce Park , Cara Monastra , Lucas A. Pardo , Sarah Jenison , David B. Weiner

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引用次数: 0

摘要

目前的流感疫苗大多诱导毒株特异性免疫，需要每年重新配制和给药。在这里，我们基于A/H1N1/Wisconsin/588/2019开发了一种改进型季节性流感疫苗。我们设计了一种dna启动的自组装纳米颗粒，该纳米颗粒显示了七个威斯康星/588/2019血凝素（HA）头部结构域（WI19-7mer）。WI19-7mer纳米疫苗比DNA编码的HA三聚体（WI19 - HA）提高了小鼠的异源HAI滴度和CD8+细胞反应。在人类抗体库小鼠中，与WI19 HA免疫的动物相比，WI19-7mer诱导了对多种H1 - HA的更大的广度。WI19-7mer免疫小鼠的交叉反应性HAI滴度比WI19 HA维持得更好。与挑战匹配的HA三聚体相比，WI19-7mer诱导了更高的抗体结合宽度，并在异源攻击中提供了更好的保护。在WI19-7mer中添加细胞因子佐剂（CTACK）可显著改善宽度、HAI、外周反应和在异源攻击中的保护作用。这些数据表明，结合核酸递送、免疫聚焦、低价纳米颗粒和粘膜佐剂来增强疫苗有效性对其他病毒具有更广泛的应用。

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DNA co-delivery of seasonal H1 influenza hemagglutinin nanoparticle vaccines with chemokine adjuvant CTACK induces potent immunogenicity for heterologous protection in vivo

Current influenza vaccines induce mostly strain-specific immunity necessitating annual reformulation and dosing. Here, we developed an improved seasonal influenza vaccine based on A/H1N1/Wisconsin/588/2019. We designed a DNA-launched self-assembling nanoparticle that displayed seven Wisconsin/588/2019 hemagglutinin (HA) head domains (WI19-7mer). WI19-7mer nanovaccine improved heterologous HAI titers and CD8+ cellular responses in mice than DNA encoded HA trimer (WI19 HA). In human antibody repertoire mice, WI19-7mer induced superior breadth to a diverse panel of H1 HAs compared to WI19 HA immunized animals. Cross-reactive HAI titers were maintained better in mice immunized with WI19-7mer than WI19 HA. The WI19-7mer induced improved antibody binding breadth and provided superior protection in a heterologous challenge compared to challenge-matched HA trimer. Addition of the cytokine adjuvant (CTACK) to WI19-7mer significantly improved breadth, HAI, peripheral responses, and protection in heterologous challenge. These data demonstrate that combining nucleic acid delivery, immune focusing, low valency nanoparticle, and mucosal adjuvant for enhanced vaccine effectiveness has broader applications for other viruses.

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

期刊介绍： Vaccine is unique in publishing the highest quality science across all disciplines relevant to the field of vaccinology - all original article submissions across basic and clinical research, vaccine manufacturing, history, public policy, behavioral science and ethics, social sciences, safety, and many other related areas are welcomed. The submission categories as given in the Guide for Authors indicate where we receive the most papers. Papers outside these major areas are also welcome and authors are encouraged to contact us with specific questions.