Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok (R)) against influenza in healthy adults: A randomized, placebo-controlled trial

University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. John
Vaccine (Impact Factor: 3.62). 08/2011; 29(44):7733-9. DOI: 10.1016/j.vaccine.2011.07.128
Source: PubMed


Development of influenza vaccines that do not use embryonated eggs as the substrate for vaccine production is a high priority. We conducted this study to determine the protective efficacy a recombinant, baculovirus-expressed seasonal trivalent influenza virus hemagglutinin (rHA0) vaccine (FluBlok(®)).
Healthy adult subjects at 24 centers across the US were randomly assigned to receive a single injection of saline placebo (2304 subjects), or trivalent FluBlok containing 45 mcg of each rHA0 component (2344 subjects). Serum samples for assessment of immune responses by hemagglutination-inhibition (HAI) were taken from a subset of subjects before and 28 days after immunization. Subjects were followed during the 2007-2008 influenza season and combined nasal and throat swabs for virus isolation were obtained from subjects reporting influenza-like illness.
Rates of local and systemic side effects were low, and the rates of systemic side effects were similar in the vaccine and placebo groups. HAI antibody responses were seen in 78%, 81%, and 52% of FluBlok recipients to the H1, H3, and B components, respectively. FluBlok was 44.6% (95% CI, 18.8%, 62.6%) effective in preventing culture-confirmed influenza meeting the CDC influenza-like illness case definition despite significant antigenic mismatch between the vaccine antigens and circulating viruses.
Trivalent rHA0 vaccine was safe, immunogenic and effective in the prevention of culture confirmed influenza illness, including protection against drift variants.

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    • "Several cultivated insect cell lines are important hosts for the heterologous expression of recombinant proteins for various research applications (Cherezov et al., 2007; Imasaki et al., 2011; Rasmussen et al., 2007; White et al., 2012) and of virus-like particles (VLPs) as vaccines (Metz and Pijlman, 2011; Shrestha et al., 2007; Treanor et al., 2011; Vicente et al., 2011). Predominantly, these processes are performed via infection of lepidopteran-derived cell lines with the baculovirus expression vector system (BEVS) (Berger et al., 2004; Jarvis, 2009; Kost et al., 2005; Summers, 2006). "
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    ABSTRACT: The High Five (H5) cell line, derived from the lepidopteran Trichoplusia ni, is one of the major insect cell hosts for the production of recombinant proteins using the baculovirus expression vector system (BEVS). Here, we describe a simple polyethylenimine (PEI)-based transient gene expression (TGE) process for the rapid production of recombinant proteins from suspension-adapted H5 cells. The method was optimized using two model proteins, enhanced green fluorescent protein (EGFP) and human tumor necrosis factor receptor-Fc fusion protein (TNFR-Fc). After screening several promoter and enhancer combinations for high levels of TNFR:Fc production, an expression vector containing the Autographa californica multicapsid nucleopolyhedrovirus immediate early 1 (ie1) promoter and homologous region 5 (hr5) enhancer was selected. Cells were transfected at a density of 2 × 10(6) cells/mL by direct addition of DNA and PEI. Under optimized conditions, a 90% transfection efficiency (percentage of EGFP-positive cells) was obtained. In addition, we observed volumetric TNFR-Fc yields over 150 μg/mL within 4 days of transfection. The method was found to be reproducible and scalable to 300 mL. This plasmid-based transient transfection process is a simple and efficient alternative to the BEVS for recombinant protein production in H5 cells.
    Journal of Biotechnology 10/2015; 216. DOI:10.1016/j.jbiotec.2015.10.007 · 2.87 Impact Factor
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    • "Advances in molecular biology and recombinant technologies have opened avenues for the design and development of new influenza vaccines which attempt to address these limitations. These technologies include subunit vaccines based on recombinant baculovirus expressed hemagglutinin (HA) in insect cells [5] [6]; bacterially produced globular HA domain fused to flagellin [7] [8]; nucleic acid based vaccines [9] [10]; virosomes (liposomes containing influenza surface antigens) [11] and recombinant virus-like particles (VLPs) produced in plant-or insect cells [12] [13]. Meanwhile; with several VLP-based blockbuster vaccines against human papillomavirus and hepatitis on the market; the VLP technology has proven its great benefits [14] [15]. "
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    Vaccine 07/2014; 32(39). DOI:10.1016/j.vaccine.2014.07.011 · 3.62 Impact Factor
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    • "However, there are some disadvantages, such as non-mammalian-like protein glycosylation and the presence of high titers of contaminating baculovirus particles and Sf9 cell debris in the expression supernatants (Krammer et al., 2010). The new trivalent seasonal influenza vaccine ''Flublok'' which contains a mixture of three recombinant hemagglutinins (rHAs) from two influenza A strains H1N1 and H3N2 and one influenza B strain that have been expressed in baculovirus was proved to be safe, immunogenic and effective in the prevention of laboratoryconfirmed influenza illness (Treanor et al., 2011). For the investigation of the vaccine potential of Bac-HA, groups of mice were immunized by subcutaneous (s.c.) or intranasal (i.n.) routes and challenged with mouse-adapted reassortant H6(Shorebird) virus. "
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