title: Immunologic characterization of a novel inactivated nasal mumps virus vaccine adjuvanted with Protollin.
abstract: An inactivated, mucosal mumps virus (MuV) vaccine would address many of the problems associated with current live-attenuated formulations. Protollin (Prl)-based adjuvants (containing TLR2 and TLR4 ligands) are well-suited for nasal administration. We sought to develop an inactivated whole-virus nasal vaccine for MuV using the Prl adjuvant/delivery vehicle and to test tolerability and immunogenicity in a mouse model. BALB/c mice exhibited signs of transient reactogenicity (hunched posture, erect fur, weight loss ≤10% of total body weight) following administration of intranasal MuV-Prl vaccines, though most of these manifestations resolved within 24h. Compared to high-dose unadjuvanted vaccine (8μgMuV), administration of high-dose adjuvanted formulation (8μgMuV-Prl) induced greater MuV-specific serum IgG (3.26E6ng/mL vs. 2.2E5ng/mL, 8μgMuV-Prl vs. 8μgMuV, p<0.001) and mucosal IgA (128ng/mL vs. 45ng/mL, 8μgMuV-Prl vs. 8μgMuV, p<0.05). Serum IgG isotypes and splenocyte cytokine secretion induced by MuV-Prl suggested a predominant T helper cell (Th)1-type immune response. This response was characterized by: (1) ≥four-fold increase of IgG2a levels compared to IgG1; and (2) high IL-2 (644pg/mL)/IFN-γ (228pg/mL) and low IL-5 (31pg/mL) secretion in MuV-restimulated splenocytes from animals receiving MuV-Prl formulations. MuV-Prl vaccination induced higher levels of serum antibodies capable of neutralizing MuV in vitro than MuV alone, particularly for high-dose 8μg formulations (357 neutralizing units (NU)/mL vs. 32NU/mL, 8μgMuV-Prl vs. 8μgMuV, p<0.001). Thus, nasal MuV-Prl vaccines are fairly well-tolerated and highly immunogenic in mice.
authors.affiliation: Research Institute of the McGill University Health Centre, Department of Infectious Diseases, McGill University, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. Electronic address: katie.young@mail.mcgill.ca.
authors.forename: Katie R
authors.initials: KR
authors.lastname: Young
authors.affiliation: Research Institute of the McGill University Health Centre, Department of Infectious Diseases, McGill University, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. Electronic address: snzula@gmail.com.
authors.forename: Sazini
authors.initials: S
authors.lastname: Nzula
authors.affiliation: GlaxoSmithKline Biologicals of North America, 525 Cartier Blvd. West, Laval, Quebec, Canada H7V 3S8. Electronic address: david.s.burt@gsk.com.
authors.forename: David S
authors.initials: DS
authors.lastname: Burt
authors.affiliation: Research Institute of the McGill University Health Centre, Department of Infectious Diseases, McGill University, 1650 Cedar Ave., Montreal, Quebec, Canada H3G 1A4. Electronic address: brian.ward@mail.mcgill.ca.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Ward
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000281:Administration, Intranasal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000917:Antibody Formation; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology*; D016207:Cytokines / Q000276:immunology; D004338:Drug Combinations; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009107:Mumps / Q000517:prevention & control; D009108:Mumps Vaccine / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D016207:Cytokines; D004338:Drug Combinations; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D009108:Mumps Vaccine; C493785:Protollin; D015164:Vaccines, Inactivated; D003546:Cysteine Endopeptidases
keywords: Adjuvant; Mumps virus; Proteosome; Protollin; Vaccine