Kang Sang-Moo, Yoo Dae-Goon, Lipatov Aleksandr S, Song Jae-Min, Davis C Todd, Quan Fu-Shi, Chen Li-Mei, Donis Ruben O, Compans Richard W
Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
PLoS One. 2009;4(3):e4667. doi: 10.1371/journal.pone.0004667. Epub 2009 Mar 2.
Recurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.
METHODOLOGY/PRINCIPAL FINDINGS: Influenza virus-like particles (VLPs) produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1) hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.
CONCLUSIONS/SIGNIFICANCE: These results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.
高致病性H5N1禽流感病毒的反复爆发对最终引发大流行构成威胁。对人群进行早期疫苗接种将是控制新出现的流感大流行的最有效措施。
方法/主要发现：在昆虫细胞培养底物中产生的流感病毒样颗粒（VLP）在疫苗生产中不依赖于受精鸡蛋的供应。我们制备了含有甲型流感病毒/越南1203/04（H5N1）血凝素、神经氨酸酶和基质蛋白的VLP，并研究了它们的临床前免疫原性和保护效果。用H5N1 VLP经鼻免疫的小鼠产生了高水平的H5N1特异性抗体，并且在免疫后30周对高剂量的同源H5N1病毒感染具有100%的保护作用。体内和体外对病毒抗原再刺激的快速回忆反应证明，这种保护可能与全身和粘膜部位的体液和细胞免疫记忆相关。
结论/意义：这些结果为将H5N1 VLP疫苗接种作为减轻H5N1流感可能大流行的公共卫生干预措施进行临床评估提供了支持。
