Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.
Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.
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用于佐剂制剂的脂质纳米颗粒组合物在QIV疫苗接种的小鼠中调节流感病毒感染后的疾病。
DOI：
10.1101/2024.01.14.575599
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Schotsaert,Michael
中科院分区：
文献类型：
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作者：
Jangra,Sonia;Lamoot,Alexander;Singh,Gagandeep;Laghlali,Gabriel;Chen,Yong;Yz,Tingting;García-Sastre,Adolfo;DeGeest,BrunoG;Schotsaert,Michael
佐剂可以增强目前许可的流感疫苗的疫苗效力。我们在小鼠模型中测试了使用两种佐剂的流感疫苗接种：仙台病毒衍生的缺陷干扰 (SDI) RNA、RIG-I 激动剂和两亲性咪唑喹啉 (IMDQ-PEG-Chol)、TLR7/8 佐剂。带负电荷的 SDI RNA 被配制成脂质纳米粒子 (LNP)，促进 RIG-I 激动剂直接递送至细胞质。我们之前曾测试过 SDI 和 IMDQ-PEG-Chol 作为流感和 SARS-CoV-2 疫苗的独立佐剂和组合佐剂。在这里，我们针对 LNP 配方测试了两种不同的可电离脂质：K-Ac7-Dsa 和 S-Ac7-Dog。在许可的疫苗环境（四价流感疫苗或 QIV）中，针对 H1N1 流感病毒验证了含有或不含空或 SDI 负载 LNP 的 IMDQ-PEG-Chol 的佐剂作用，显示出对抗体滴度和 T 细胞反应的强烈诱导。根据佐剂组合和 LNP 脂质组成（K-Ac7-Dsa 或 S-Ac7-Dog 脂质），可以针对 1 型或 2 型宿主反应定制体液和细胞疫苗反应，并具有与病毒感染期间的保护相关的特定细胞因子谱。针对 H1N1 甲型流感病毒疫苗匹配株的攻击，检查了不同疫苗/LNP/佐剂组合所赋予的保护程度。接受用 SDI、IMDQ-PEG-Chol 或两者配制的 LNP 的组在病毒感染后五天时，其肺部的病毒复制水平非常低。 LNP 可电离的脂质成分以及负载（空与 SDI）也会影响宿主对感染的反应，这反映在感染后接种疫苗的动物肺部的细胞因子和趋化因子水平。这些研究显示了 LNP 作为许可疫苗的佐剂递送载体的潜力，并说明了 LNP 成分对于随后宿主对感染反应的重要性，这是疫苗安全性的一个重要考虑点。
Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), TLR7/8 adjuvant. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating the direct delivery of a RIG-I agonist to the cytosol. We have previously tested SDI and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated in a licensed vaccine setting (quadrivalent influenza vaccine or QIV) against H1N1 influenza virus, showing robust induction of antibody titres and T cell responses. Depending on the adjuvant combination and LNP lipid composition (K-Ac7-Dsa or S-Ac7-Dog lipids), humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with protection during viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was examined against challenge with the vaccine-matching strain of H1N1 influenza A virus. Groups that received either LNP formulated with SDI, IMDQ-PEG-Chol or both showed very low levels of viral replication in their lungs at five days post virus infection. LNP ionizable lipid composition as well as loading (empty versus SDI) also skewed host responses to infection, as reflected in the cytokine and chemokine levels in lungs of vaccinated animals upon infection. These studies show the potential of LNPs as adjuvant delivery vehicles for licensed vaccines and illustrate the importance of LNP composition for subsequent host responses to infection, an important point of consideration for vaccine safety.