title: Truncated recombinant Dobrava hantavirus nucleocapsid proteins induce strong, long-lasting immune responses in mice.
abstract: We describe the cloning and expression of Dobrava hantavirus (DOBV) nucleocapsid proteins and a truncated form consisting of the first 118 N-terminal amino acids, and the capacity of these E. coli ICONE 200-expressed recombinant proteins (rNp) to induce a protective immune response against DOBV in mice. As an alternative carrier protein, the outer membrane protein A derived from Klebsiella pneumoniae (rP40) has been coupled to different rNp constructs. All recombinant proteins were found to be highly immunogenic after three immunizations of rNp. The immunizations resulted in the induction of a strong Np-specific IgG response with a predominance of IgG1 over IgG2b and IgG2a, suggesting a mixed Th1/Th2 cell involvement. A specific IgG3 response could not be detected. Mice immunized with recombinant DOBV rNp without rP40 showed lower nucleocapsid-specific antibody responses in comparison with the rP40-conjugated constructs, but all mice were found to be protected against DOBV challenge. Our results indicate that the rNp constructs coupled to rP40, represent promising vaccine candidates.
authors.affiliation: Laboratory of Clinical and Epidemiological Virology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium.
authors.forename: Piet
authors.initials: P
authors.lastname: Maes
authors.forename: Els
authors.initials: E
authors.lastname: Keyaerts
authors.forename: Véronique
authors.initials: V
authors.lastname: Bonnet
authors.forename: Jan
authors.initials: J
authors.lastname: Clement
authors.forename: Tatjana
authors.initials: T
authors.lastname: Avsic-Zupanc
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Marc
authors.initials: M
authors.lastname: Van Ranst
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D018063:Hantaan virus / Q000276:immunology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000276:immunology*; D007114:Immunization; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007279:Injections, Subcutaneous; D007711:Klebsiella pneumoniae / Q000737:chemistry; D051379:Mice; D019590:Nucleocapsid Proteins / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; D019590:Nucleocapsid Proteins; D011994:Recombinant Proteins; C078167:OMPA outer membrane proteins