FluBlok, a recombinant hemagglutinin influenza vaccine

Protein Sciences Corporation, 1000 Research Parkway, Meriden, CT 06450, USA.
Influenza and Other Respiratory Viruses (Impact Factor: 2.2). 12/2008; 2(6):211-9. DOI: 10.1111/j.1750-2659.2008.00053.x
Source: PubMed


FluBlok, a recombinant trivalent hemagglutinin (HA) vaccine produced in insect cell culture using the baculovirus expression system, provides an attractive alternative to the current egg-based trivalent inactivated influenza vaccine (TIV) manufacturing process. FluBlok contains three times more HA than TIV and does not contain egg-protein or preservatives. This review discusses the four main clinical studies that were used to support licensure of FluBlok under the 'Accelerated Approval' mechanism in the United States.

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Available from: Peter Patriarca, Feb 16, 2015
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    • "This process is iterative and often time-consuming, and occasionally requires selection of an HA that is less than optimally matched to the HA of predominantly circulating strains [5]. The development of recombinant HA-based vaccines offer the potential for overcoming these limitations [6], but some observers remain concerned that HA-based vaccines could be inadequately effective, especially in vulnerable populations such as the elderly, who appear to be a critical target population for A(H7N9)-mediated severe disease [7]. An A(H7N9) vaccine candidate was constructed from full length, unmodified influenza hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 strain and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) strain. "
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    ABSTRACT: The recent emergence of severe human illness caused by avian-origin influenza A(H7N9) viruses in China has precipitated a global effort to rapidly develop and test vaccine candidates. To date, non-A(H7N9) H7 subtype influenza vaccine candidates have been poorly immunogenic and difficulties in production of A(H7N9) virus seed strains have been encountered. A candidate recombinant A(H7N9) vaccine consisting of full length, unmodified hemagglutinin (HA) and neuraminidase (NA) from the A/Anhui/1/2013 and the matrix 1 (M1) protein from the A/Indonesia/05/2005 (H5N1) were cloned into a baculovirus vector. Baculovirus infected Spodoptera frugiperda (Sf9) insect cells secreted virus like particles (VLP) composed of HA, NA, and M1 that resemble mature influenza virions. Genetic construction of vaccine from acquisition of an H7N9 genomic sequence to production of A(H7N9) VLP occurred in 26 days. The immunogenicity and efficacy of A/Anhui/1/2013 (H7N9) VLP vaccine administered on days 0 and 14 were evaluated in a lethal wild-type challenge Balb/c mouse model. Control groups included a non-homologous H7 vaccine (A/chicken/Jalisco/CPA1/2012 (H7N3)-VLP), and A/Indonesia/05/2005 (H5N1)-VLP, or placebo. All vaccines were administered with or without ISCOMATRIX. A(H7N9) VLP elicited hemagglutination-inhibition (HAI) antibody titers of ≥1:64 against the homologous virus, cross-reactive HAI against the heterologous A(H7N3), and 3- to 4-fold higher HAI responses in corresponding ISCOMATRIX subgroups. Similarly, all doses of H7N9 VLP elicited anti-neuraminidase (NA) antibody, with 3- to 4-fold higher responses measured in the corresponding ISCOMATRIX subgroups. The non-homologous H7 vaccine induced both H7N3 and H7N9 HAI but no N9 anti-NA antibodies. A lethal murine wild-type A/Anhui/1/2013 (H7N9) challenge demonstrated 100% survival of all animals receiving A(H7N9) and A(H7N3) vaccine, versus 0% survival in A(H5N1) vaccine and placebo groups. Together, the data demonstrate that recombinant H7N9 vaccine can be rapidly developed that was immunogenic and efficacious supporting testing in man as a pandemic influenza H7N9 vaccine candidate.
    Vaccine 07/2013; 31(40). DOI:10.1016/j.vaccine.2013.07.043 · 3.62 Impact Factor
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    • "The production of purified recombinant hemagglutinin (rHA) subunit vaccines via the baculovirus expression vector system (BEVS) is a leading alternative platform for influenza vaccine manufacture. The most advanced influenza vaccine candidate produced using this technology (under the trade name Flublok®) is a trivalent composition of three rHA proteins corresponding to the full length HA proteins of the seasonally circulating influenza strains [8-11]. Clinical trials of Flublok have demonstrated that the vaccine is well-tolerated, immunogenic (as assessed by the induction of hemagglutination inhibiting [HAI] antibodies), and provides protection against drifted influenza viruses [8-10]. "
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    ABSTRACT: Background The recent H1N1 influenza pandemic illustrated the shortcomings of the vaccine manufacturing process. The A/California/07/2009 H1N1 pandemic influenza vaccine or A(H1N1)pdm09 was available late and in short supply as a result of delays in production caused by low yields and poor antigen stability. Recombinant technology offers the opportunity to shorten manufacturing time. A trivalent recombinant hemagglutinin (rHA) vaccine candidate for seasonal influenza produced using the baculovirus expression vector system (BEVS) was shown to be as effective and safe as egg-derived trivalent inactivated vaccine (TIV) in human clinical studies. In this study, we describe the characterization of the A/California/07/2009 rHA protein and compare the H1N1 pandemic rHA to other seasonal rHA proteins. Results Our data show that, like other rHA proteins, purified A/California/07/2009 rHA forms multimeric rosette-like particles of 20–40 nm that are biologically active and immunogenic in mice as assayed by hemagglutination inhibition (HAI) antibody titers. However, proteolytic digest analysis revealed that A/California/07/2009 rHA is more susceptible to proteolytic degradation than rHA proteins derived from other seasonal influenza viruses. We identified a specific proteolytic site conserved across multiple hemagglutinin (HA) proteins that is likely more accessible in A/California/07/2009 HA, possibly as a result of differences in its protein structure, and may contribute to lower antigen stability. Conclusion We conclude that, similar to the recombinant seasonal influenza vaccine, recombinant A(H1N1)pdm09 vaccine is likely to perform comparably to licensed A(H1N1)pdm09 vaccines and could offer manufacturing advantages.
    BMC Biotechnology 10/2012; 12(1):77. DOI:10.1186/1472-6750-12-77 · 2.03 Impact Factor
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    • "Despite the widespread use of recombinant HA in the field, expression and purification methods for HA vary greatly. Full length or truncation mutants have been expressed using a variety of expression systems [18]–[21]. The biochemical and antigenic characteristics of the produced reagents are therefore influenced by the sequence of the HA expression construct, the production system and the purification method. "
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    ABSTRACT: Recently, a new class of broadly neutralizing anti-influenza virus antibodies that target the stalk domain of the viral hemagglutinin was discovered. As such, induction, isolation, characterization, and quantification of these novel antibodies has become an area of intense research and great interest. Since most of these antibodies bind to conformational epitopes, the structural integrity of hemagglutinin substrates for the detection and quantification of these antibodies is of high importance. Here we evaluate the binding of these antibodies to soluble, secreted hemagglutinins with or without a carboxy-terminal trimerization domain based on the natural trimerization domain of T4 phage fibritin. The lack of such a domain completely abolishes binding to group 1 hemagglutinins and also affects binding to group 2 hemagglutinins. Additionally, the presence of a trimerization domain positively influences soluble hemagglutinin stability during expression and purification. Our findings suggest that a carboxy-terminal trimerization domain is a necessary requirement for the structural integrity of stalk epitopes on recombinant soluble influenza virus hemagglutinin.
    PLoS ONE 08/2012; 7(8):e43603. DOI:10.1371/journal.pone.0043603 · 3.23 Impact Factor
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