Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus
Virus-like particle vaccine induces protective immunity against homologous and heterologous strains of influenza virus
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DOI：
10.1128/jvi.02052-06
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Kang, Sang-Moo
中科院分区：
文献类型：
--
作者：
Quan, Fu-Shi;Huang, Chunzi;Kang, Sang-Moo
高致病性禽流感病毒的反复爆发构成了致命疾病大流行的威胁，因此开发安全有效的疫苗成为当务之急。流感病毒样颗粒（VLP）被认为是一种有前途的疫苗方法。然而，VLP 诱导的免疫反应及其在诱导记忆免疫反应和交叉保护免疫中的作用尚未得到研究。在这项研究中，我们开发了含有流感病毒 A/PR8/34 (H1N1) 血凝素 (HA) 和基质 (M1) 蛋白的 VLP，并研究了它们的免疫原性、长期交叉保护功效以及对小鼠肺部促炎细胞因子的影响。使用含有 HA 的 VLP 进行鼻内免疫可诱导高血清和粘膜抗体滴度以及针对 PR8 和 A/WSN/33 (H1N1) 病毒的中和活性。用含有HA的VLP免疫的小鼠几乎没有或没有显示促炎性肺细胞因子，并且即使在免疫后5个月也能免受小鼠适应性PR8或WSN病毒的致命攻击。流感病毒颗粒诱导粘膜免疫球蛋白 G 和细胞免疫反应，这些反应在病毒攻击后迅速重新激活。在免疫小鼠的骨髓中检测到了长寿的抗体分泌细胞。鼻内施用的免疫血清能够对 PR8 或 WSN 的致命攻击提供 100% 的保护，这进一步证明抗 HA 抗体主要负责预防感染。总而言之，这些结果表明，非复制型流感 VLP 代表了开发安全有效的疫苗来控制致命流感病毒传播的一种有前景的策略。
Recurrent outbreaks of highly pathogenic avian influenza virus pose the threat of pandemic spread of lethal disease and make it a priority to develop safe and effective vaccines. Influenza virus-like particles (VLPs) have been suggested to be a promising vaccine approach. However, VLP-induced immune responses, and their roles in inducing memory immune responses and cross-protective immunity have not been investigated. In this study, we developed VLPs containing influenza virus A/PR8/34 (H1N1) hemagglutinin (HA) and matrix (M1) proteins and investigated their immunogenicity, long-term cross-protective efficacy, and effects on lung proinflammatory cytokines in mice. Intranasal immunization with VLPs containing HA induced high serum and mucosal antibody titers and neutralizing activity against PR8 and A/WSN/33 (H1N1) viruses. Mice immunized with VLPs containing HA showed little or no proinflammatory lung cytokines and were protected from a lethal challenge with mouse-adapted PR8 or WSN viruses even 5 months postimmunization. Influenza VLPs induced mucosal immunoglobulin G and cellular immune responses, which were reactivated rapidly upon virus challenge. Long-lived antibody-secreting cells were detected in the bone marrow of immunized mice. Immune sera administered intranasally were able to confer 100% protection from a lethal challenge with PR8 or WSN, which provides further evidence that anti-HA antibodies are primarily responsible for preventing infection. Taken together, these results indicate that nonreplicating influenza VLPs represent a promising strategy for the development of a safe and effective vaccine to control the spread of lethal influenza viruses.