Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge
Intranasal Vaccination with 1918 Influenza Virus-Like Particles Protects Mice and Ferrets from Lethal 1918 and H5N1 Influenza Virus Challenge
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DOI：
10.1128/jvi.00207-09
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发表时间：
2009-06-01
影响因子：
5.4
通讯作者：
Tumpey, Terrence M.
中科院分区：
文献类型：
--
作者：
Perrone, Lucy A.;Ahmad, Attiya;Tumpey, Terrence M.
能够诱导交叉反应或异型免疫的流感疫苗可能是预防新型亚型病毒的重要第一线。流感病毒样颗粒（VLP）展示功能性病毒蛋白是有效的疫苗针对复制能力同源病毒，但他们的能力，诱导异型免疫尚未得到充分的测试。为了测量VLP疫苗针对已知流感大流行病毒的效力，从1918 H1N1病毒的结构蛋白产生重组VLP。比较了H1N1 VLP的粘膜给药和传统胃肠外给药对重建的1918年病毒和从致命的人类病例中分离的高致病性禽H5N1病毒的保护能力。接受两次H1N1 VLP鼻内免疫的小鼠在很大程度上受到保护，免受1918病毒和H5N1病毒的致命攻击。相比之下，接受1918个VLP的两次肌内免疫的小鼠仅保护免受同源病毒攻击。用1918 VLP接种小鼠的粘液瘤疫苗诱导的交叉反应性免疫球蛋白G（IgG）和伊加抗体水平高于胃肠外疫苗接种。类似地，用1918个VLP粘膜接种的雪貂在H5N1病毒的致命攻击中完全存活，而在肠胃外接种的动物中仅观察到50%的存活率。这些结果表明，VLP疫苗接种的战略，对大流行病毒和刺激异型免疫力对流感病毒株威胁大流行的潜力。
Influenza vaccines capable of inducing cross-reactive or heterotypic immunity could be an important first line of prevention against a novel subtype virus. Influenza virus-like particles (VLPs) displaying functional viral proteins are effective vaccines against replication-competent homologous virus, but their ability to induce heterotypic immunity has not been adequately tested. To measure VLP vaccine efficacy against a known influenza pandemic virus, recombinant VLPs were generated from structural proteins of the 1918 H1N1 virus. Mucosal and traditional parenteral administrations of H1N1 VLPs were compared for the ability to protect against the reconstructed 1918 virus and a highly pathogenic avian H5N1 virus isolated from a fatal human case. Mice that received two intranasal immunizations of H1N1 VLPs were largely protected against a lethal challenge with both the 1918 virus and the H5N1 virus. In contrast, mice that received two intramuscular immunizations of 1918 VLPs were only protected against a homologous virus challenge. Mucosal vaccination of mice with 1918 VLPs induced higher levels of cross-reactive immunoglobulin G (IgG) and IgA antibodies than did parenteral vaccination. Similarly, ferrets mucosally vaccinated with 1918 VLPs completely survived a lethal challenge with the H5N1 virus, while only a 50% survival rate was observed in parenterally vaccinated animals. These results suggest a strategy of VLP vaccination against a pandemic virus and one that stimulates heterotypic immunity against an influenza virus strain with threatening pandemic potential.