Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
PLoS One. 2009 Jun 24;4(6):e6032. doi: 10.1371/journal.pone.0006032.
There is need for improved human influenza vaccines, particularly for older adults who are at greatest risk for severe disease, as well as to address the continuous antigenic drift within circulating human subtypes of influenza virus. We have engineered an influenza virus-like particle (VLP) as a new generation vaccine candidate purified from the supernatants of Sf9 insect cells following infection by recombinant baculoviruses to express three influenza virus proteins, hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1). In this study, a seasonal trivalent VLP vaccine (TVV) formulation, composed of influenza A H1N1 and H3N2 and influenza B VLPs, was evaluated in mice and ferrets for the ability to elicit antigen-specific immune responses. Animals vaccinated with the TVV formulation had hemagglutination-inhibition (HAI) antibody titers against all three homologous influenza virus strains, as well as HAI antibodies against a panel of heterologous influenza viruses. HAI titers elicited by the TVV were statistically similar to HAI titers elicited in animals vaccinated with the corresponding monovalent VLP. Mice vaccinated with the TVV had higher level of influenza specific CD8+ T cell responses than a commercial trivalent inactivated vaccine (TIV). Ferrets vaccinated with the highest dose of the VLP vaccine and then challenged with the homologous H3N2 virus had the lowest titers of replicating virus in nasal washes and showed no signs of disease. Overall, a trivalent VLP vaccine elicits a broad array of immunity and can protect against influenza virus challenge.
需要改进人类流感疫苗，特别是针对老年人的疫苗，因为他们患重病的风险最高，并且要解决循环中的人类流感病毒亚型的持续抗原漂移问题。我们已经设计了一种流感病毒样颗粒（VLP）作为新一代候选疫苗，该疫苗是从感染重组杆状病毒的 Sf9 昆虫细胞上清液中纯化而来的，可表达三种流感病毒蛋白，血凝素（HA），神经氨酸酶（NA）和基质 1（M1）。在这项研究中，评估了一种季节性三价 VLP 疫苗（TVV）配方，该配方由流感 A H1N1 和 H3N2 以及流感 B VLP 组成，用于评估其在小鼠和雪貂中引起抗原特异性免疫应答的能力。接种 TVV 疫苗的动物对所有三种同源流感病毒株均具有血凝抑制（HAI）抗体滴度，并且对一组异源流感病毒也具有 HAI 抗体。 TVV 引起的 HAI 滴度与接种相应单价 VLP 的动物引起的 HAI 滴度统计学上相似。接种 TVV 的小鼠比商业三价灭活疫苗（TIV）具有更高水平的流感特异性 CD8+T 细胞反应。接种最高剂量 VLP 疫苗然后用同源 H3N2 病毒攻击的雪貂在鼻洗液中复制病毒的滴度最低，并且没有疾病迹象。总体而言，三价 VLP 疫苗可引发广泛的免疫反应，并能预防流感病毒的攻击。
