title: Adjuvant effect of the human metapneumovirus (HMPV) matrix protein in HMPV subunit vaccines.
abstract: The human metapneumovirus (HMPV) fusion (F) protein is the most immunodominant protein, yet subunit vaccines containing only this protein do not confer complete protection. The HMPV matrix (M) protein induces the maturation of antigen-presenting cells in vitro. The inclusion of the M protein into an F protein subunit vaccine might therefore provide an adjuvant effect. We administered the F protein twice intramuscularly, adjuvanted with alum, the M protein or both, to BALB/c mice at 3 week intervals. Three weeks after the boost, mice were infected with HMPV and monitored for 14 days. At day 5 post-challenge, pulmonary viral titres, histopathology and cytokine levels were analysed. Mice immunized with F+alum and F+M+alum generated significantly more neutralizing antibodies than mice immunized with F only [titres of 47 ± 7 (P<0.01) and 147 ± 13 (P<0.001) versus 17 ± 2]. Unlike F only [1.6 ± 0.5 × 10(3) TCID50 (g lung)(-1)], pulmonary viral titres in mice immunized with F+M and F+M+alum were undetectable. Mice immunized with F+M presented the most important reduction in pulmonary inflammation and the lowest T-helper Th2/Th1 cytokine ratio. In conclusion, addition of the HMPV-M protein to an F protein-based vaccine modulated both humoral and cellular immune responses to subsequent infection, thereby increasing the protection conferred by the vaccine.
authors.affiliation: Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aerts
authors.affiliation: Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
authors.forename: Chantal
authors.initials: C
authors.lastname: Rhéaume
authors.affiliation: Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
authors.forename: Julie
authors.initials: J
authors.lastname: Carbonneau
authors.affiliation: Department of Anatomo-pathology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec G1V 4G5, Canada.
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavigne
authors.affiliation: Department of Anatomo-pathology, Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Quebec City, Quebec G1V 4G5, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Couture
authors.affiliation: Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
authors.forename: Marie-Ève
authors.initials: MÈ
authors.lastname: Hamelin
authors.affiliation: Centre de Recherche en Infectiologie du Centre Hospitalier Universitaire de Québec and Université Laval, Quebec City, Quebec G1V 4G2, Canada.
authors.forename: Guy
authors.initials: G
authors.lastname: Boivin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000938:Antigen-Presenting Cells; D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007114:Immunization / Q000379:methods; D008168:Lung / Q000276:immunology / Q000821:virology; D029121:Metapneumovirus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018184:Paramyxoviridae Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology; D014763:Viral Matrix Proteins / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D022223:Vaccines, Subunit; D014763:Viral Matrix Proteins; D014765:Viral Vaccines