Kenny Roose

Publications (7)27.85 Total impact

• Article: Hepatitis B core-based virus-like particles to present heterologous epitopes.

  Kenny Roose, Sarah De Baets, Bert Schepens, Xavier Saelens
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  ABSTRACT: Since the first effort to recombinantly express the hepatitis B core protein (HBc) in bacteria, the remarkable virion-like structure has fuelled interest in unraveling the structural and antigenic properties of this protein. Initial studies proved HBc virus-like particles to possess strong immunogenic properties, which can be conveyed to linked antigens. More than 35 years later, numerous studies have been performed using HBc as a carrier protein for antigens derived from over a dozen different pathogens and diseases. In this review, the authors highlight the intriguing features of HBc as carrier and antigen, illustrated by some examples and experimental results that underscore the value of HBc as an antigen-presenting platform. Two of these HBc fusions, targeting influenza A and malaria, have even progressed into clinical testing. In the future, the HBc-based virus-like particles platform will probably continue to be used for the display of poorly immunogenic antigens, mainly because virus-like particle formation by HBc capsomers is compatible with nearly any available recombinant gene expression system.
  Expert Review of Vaccines 02/2013; 12(2):183-98. · 4.25 Impact Factor
• Article: Recombinant influenza virus carrying the RSV F85-93 CTL epitope reduces respiratory syncytial virus replication in mice.

  Sarah De Baets, Bert Schepens, Koen Sedeyn, Michael Schotsaert, Kenny Roose, Pieter Bogaert, Walter Fiers, Xavier Saelens
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  ABSTRACT: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants worldwide. Despite decades of research there is still no registered vaccine available for this major pathogen. We investigated the protective efficacy of a recombinant influenza virus PR8/NA-F(85-93) that carries the RSV CD8(+) T cell epitope F(85-93) in its neuraminidase stalk. F(85-93-)specific CTLs were induced in mice after a single intranasal immunization with PR8/NA-F(85-93) virus, and these CTLs provided a significant reduction in the lung viral load upon a subsequent challenge with RSV. To avoid influenza-induced morbidity, we treated mice with M2e-specific monoclonal antibodies before PR8/NA-F(85-93) virus infection. Treatment with anti-M2e antibodies reduced the infiltration of immune cells in the lungs upon PR8/NA-F(85-93) infection, whereas formation of inducible bronchus associated lymphoid tissue was not affected. Moreover, this treatment prevented body weight loss, yet still permitted the induction of RSV F-specific T cell responses and significantly reduced RSV replication upon challenge. These results demonstrate that it is possible to take advantage of the infection-permissive protection of M2e-specific antibodies against influenza A virus to induce heterologous CD8(+) T cell mediated immunity by an influenza A virus vector expressing the RSV F(85-93) epitope.
  Journal of Virology 01/2013; · 5.40 Impact Factor
• Source

  Available from: Lorena Itatí Ibañez

  Article: M2e-Displaying Virus-Like Particles with Associated RNA Promote T Helper 1 Type Adaptive Immunity against Influenza A.

  Lorena Itatí Ibañez, Kenny Roose, Marina De Filette, Michael Schotsaert, Jessica De Sloovere, Stefan Roels, Charlotte Pollard, Bert Schepens, Johan Grooten, Walter Fiers, Xavier Saelens
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  ABSTRACT: The ectodomain of influenza A matrix protein 2 (M2e) is a candidate for a universal influenza A vaccine. We used recombinant Hepatitis B core antigen to produce virus-like particles presenting M2e (M2e-VLPs). We produced the VLPs with and without entrapped nucleic acids and compared their immunogenicity and protective efficacy. Immunization of BALB/c mice with M2e-VLPs containing nucleic acids induced a stronger, Th1-biased antibody response compared to particles lacking nucleic acids. The former also induced a stronger M2e-specific CD4(+) T cell response, as determined by ELISPOT. Mice vaccinated with alum-adjuvanted M2e-VLPs containing the nucleic acid-binding domain were better protected against influenza A virus challenge than mice vaccinated with similar particles lacking this domain, as deduced from the loss in body weight following challenge with X47 (H3N2) or PR/8 virus. Challenge of mice that had been immunized with M2e-VLPs with or without nucleic acids displayed significantly lower mortality, morbidity and lung virus titers than control-immunized groups. We conclude that nucleic acids present in M2e-VLPs correlate with improved immune protection.
  PLoS ONE 01/2013; 8(3):e59081. · 4.09 Impact Factor
• Article: Antiserum against the conserved nine amino acid N-terminal peptide of influenza A virus matrix protein 2 is not immunoprotective.

  Marina De Filette, Tine Ysenbaert, Kenny Roose, Michael Schotsaert, Stefan Roels, Els Goossens, Bert Schepens, Walter Fiers, Xavier Saelens
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  ABSTRACT: The recent emergence and rapid spread of the pandemic H1N1 swine influenza virus reminded us once again of the need for a universal influenza vaccine that can elicit heterosubtypic protection. Here, we show the superior immunogenicity and immunoprotective capacity of the full-length matrix protein 2 ectodomain (M2e) peptide coupled to keyhole limpet haemocyanin (KLH) compared with the N-terminal 9 aa residues of M2e (SP1). Immunization with M2e-KLH protected mice against a lethal challenge with influenza A virus and significantly reduced weight loss and lung virus titres. In addition, passive transfer of serum raised in rabbits against M2e-KLH protected mice against a lethal influenza virus challenge, whereas serum from rabbits immunized with SP1-KLH did not. Nevertheless, immunofluorescence staining revealed that rabbit serum raised against SP1-KLH bound specifically to infected Madin-Darby canine kidney cells. We conclude that the peptide SP1 contains an immunogenic epitope that is not sufficient for immunoprotection.
  Journal of General Virology 10/2010; 92(Pt 2):301-6. · 3.36 Impact Factor
• Article: M2e-based universal influenza A vaccine.

  Walter Fiers, Marina De Filette, Karim El Bakkouri, Bert Schepens, Kenny Roose, Michael Schotsaert, Ashley Birkett, Xavier Saelens
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  ABSTRACT: Human influenza causes substantial morbidity and mortality. Currently, licensed influenza vaccines offer satisfactory protection if they match the infecting strain, but they come with significant drawbacks. These vaccines are derived from prototype viruses, containing the hemagglutinin of influenza viruses that are likely to cause the next epidemic. Their usefulness against a future pandemic, however, remains problematic. A vaccine based on the ectodomain of influenza matrix protein 2 (M2e) could overcome these drawbacks. M2e is highly conserved in both human and avian influenza A viruses. The low immunogenicity against natural M2e can be overcome by fusing M2e to an appropriate carrier such as Hepatitis B virus-derived virus-like particles. Such chimeric particles can be produced in a simple and safe bacterial expression system, requiring minimal biocontainment, and can be obtained in a pure form. Experiments in animal models have demonstrated that M2e-based vaccines induce protection against a lethal challenge with various influenza A virus subtypes. Furthermore, the production and use of an effective M2e-vaccine could be implemented at any time regardless of seasonality, both in an epidemic as well as in a pandemic preparedness program. In animal models, M2e-vaccines administered parenterally or intranasally protect against disease and mortality following challenge with various influenza A strains. Adjuvants suitable for human use improve protection, which correlates with higher anti-M2e antibody responses of defined subtypes. Recently, Phase I clinical studies with M2e-vaccines have been completed, indicating their safety and immunogenicity. Further clinical development of this universal influenza A vaccine candidate is being pursued in order to validate its protective efficacy in humans.
  Vaccine 10/2009; 27(45):6280-3. · 3.77 Impact Factor
• Article: Pandemic preparedness: toward a universal influenza vaccine.

  Kenny Roose, Walter Fiers, Xavier Saelens
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  ABSTRACT: The possible emergence of a new influenza pandemic is considered a major threat for human health worldwide. Pandemics start by the introduction or reintroduction and spread in the human population of an influenza virus subtype against which almost nobody has protective immunity. Currently used influenza vaccines provide good protection only against antigenically matching influenza strains. However, neither the timing nor the subtype of the next pandemic virus is known. Therefore, different approaches are being pursued in anticipation of this pandemic threat. In the present article, we review approaches that aim to induce heterosubtypic immunity, that is, protection against challenge with influenza A viruses belonging to two or more subtypes. Experimental and epidemiological studies indicate that natural infection can provide some heterosubtypic immunity, possibly involving cellular immune responses directed against matrix and/or nucleoprotein as well as humoral responses against neuraminidase. Other approaches have focused on the use of conserved epitopes of the viral proteins, including matrix protein 2 ectodomain (M2e) and nucleoprotein (NP). Proof-of-concept of protection by these novel vaccines has been obtained in animal models, and promising results from several clinical trials have recently been reported. Demonstrating the efficacy of these new vaccines against a potential pandemic influenza endowed with human transmissibility remains a major challenge.
  Drug News & Perspectives 04/2009; 22(2):80-92. · 2.21 Impact Factor
• Article: An influenza A vaccine based on tetrameric ectodomain of matrix protein 2.

  Marina De Filette, Wouter Martens, Kenny Roose, Tom Deroo, Frederik Vervalle, Mostafa Bentahir, Joel Vandekerckhove, Walter Fiers, Xavier Saelens
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  ABSTRACT: Matrix protein 2 (M2) of influenza A is a tetrameric type III membrane protein that functions as a proton-selective channel. The extracellular domain (M2e) has remained nearly invariable since the first human influenza strain was isolated in 1933. By linking a modified form of the leucine zipper of the yeast transcription factor GCN4 to M2e, we obtained a recombinant tetrameric protein, M2e-tGCN4. This protein mimics the quaternary structure of the ectodomain of the natural M2 protein. M2e-tGCN4 was purified, biochemically characterized, and used to immunize BALB/c mice. High M2e-specific serum IgG antibody titers were obtained following either intraperitoneal or intranasal administration. Immunized mice were protected fully against a potentially lethal influenza A virus challenge. Antibodies raised by M2e-tGCN4 immunization specifically bound to the surface of influenza-infected cells and to an M2-expressing cell line. Using a M2e peptide competition enzyme-linked immunosorbent assay with M2-expressing cells as target, we obtained evidence that M2e-tGCN4 induces antibodies that are specific for the native tetrameric M2 ectodomain. Therefore, fusion of an oligomerization domain to the extracellular part of a transmembrane protein allows it to mimic the natural quaternary structure and can promote the induction of oligomer-specific antibodies.
  Journal of Biological Chemistry 05/2008; 283(17):11382-7. · 4.77 Impact Factor