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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    • "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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    ABSTRACT: Methods: A novel, fully bacterially produced recombinant virus-like particle (VLP) based influenza vaccine (gH1-Qbeta) against A/California/07/2009(H1N1) was tested in a double-blind, randomized phase I clinical trial at two clinical sites in Singapore. The trial evaluated the immunogenicity and safety of gH1-Qbeta in the presence or absence of alhydrogel adjuvant. Healthy adult volunteers with no or low pre-existing immunity against A/California/07/2009 (H1N1) were randomized to receive two intramuscular injections 21 days apart, with 100μg vaccine, containing 42μg hemagglutinin antigen. Antibody responses were measured before and 21 days after each immunization by hemagglutination inhibition (HAI) assays. The primary endpoint was seroconversion on Day 42, defined as percentage of subjects which reach a HAI titer ≥40 or achieve an at least 4-fold rise in HAI titer (with pre-existing immunity). The co-secondary endpoints were safety and seroconversion on Day 21. Results: A total of 84 Asian volunteers were enrolled in this study and randomized to receive the adjuvanted (n=43) or the non-adjuvanted (n=41) vaccine. Of those, 43 and 37 respectively (95%) completed the study. There were no deaths or serious adverse events reported during this trial. A total of 535 adverse events occurred during treatment with 49.5% local solicited symptoms, of mostly (76.4%) mild severity. The most common treatment-related systemic symptom was fatigue. The non-adjuvanted vaccine met all primary and secondary endpoints and showed seroconversion in 62.2% and 70.3% of participants respectively on Day 21 and Day 42. While the adjuvanted vaccine showed an increased seroconversion from 25.5% (Day 21) to 51.2% (Day 42), it did not meet the immunogenicity endpoint. Conclusion: In summary, non-adjuvanted gH1-Qbeta showed similar antibody mediated immunogenicity and a comparable safety profile in healthy humans to commercially available vaccines. These results warrant the consideration of this VLP vaccine platform for the vaccination against influenza infection (HSA CTC1300092).
    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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    Antiviral Research 06/2014; 109(1). DOI:10.1016/j.antiviral.2014.06.002 · 3.94 Impact Factor
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    • "VLP technology is relatively new and there are limited published data on their efficacy. Protein Science Corporation is developing seasonal (Flublok) and pandemic (Panblok) influenza vaccines which have shown favourable immunogenicity and tolerability during Phase I and II clinical trials [50,52,54]. Novavax’s H1N1 VLP vaccine was well tolerated and immunogenic in a phase II clinical trial carried out in more than 4000 subjects in Mexico [55]. "
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    BMC Public Health 09/2013; 13 Suppl 3(Suppl 3):S14. DOI:10.1186/1471-2458-13-S3-S14 · 2.26 Impact Factor
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