title: Adenoviral vector expressing murine β-defensin 2 enhances immunogenicity of an adenoviral vector based H5N1 influenza vaccine in aged mice.
abstract: The ability to resist infections and respond to vaccinations is greatly reduced in the older adult population owing to a general decline in innate and adaptive immune functions with aging. Over the years several strategies such as increasing the vaccine dose, number of immunizations and using adjuvants have been evaluated to improve the immunogenicity and efficacy of vaccines in the older adult population. Murine β-defensin 2 (Mbd2) has been shown to function as a molecular adjuvant by recruiting and activating immature dendritic cells (DCs), professional antigen-presenting cells (APC), to the site of the immunization. In this study, we evaluated the potential utility of Mbd2 to enhance the efficacy of an adenoviral vector-based H5N1 influenza vaccine expressing hemagglutinin (HA) and nucleoprotein (NP) (HAd-HA-NP) in an aged mouse model. Our results indicated that immunostimulation with an adenoviral vector expressing Mbd2 (HAd-Mbd2) activated DCs and significantly enhanced the humoral and cellular immune responses induced by HAd-HA-NP. Furthermore, immunostimulation with HAd-Mbd2 followed by immunization with HAd-HA-NP resulted in significantly lower virus titers in the lungs following challenge with a H5N1 influenza virus compared to the group immunized with HAd-HA-NP without immunostimulation. Overall, our results highlight the potential utility of Mbd2 as a molecular adjuvant to enhance the immunogenicity and protective efficacy of vaccines for the elderly.
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
authors.forename: Sai V
authors.initials: SV
authors.lastname: Vemula
authors.forename: Aseem
authors.initials: A
authors.lastname: Pandey
authors.forename: Neetu
authors.initials: N
authors.lastname: Singh
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Katz
authors.forename: Ruben
authors.initials: R
authors.lastname: Donis
authors.forename: Suryaprakash
authors.initials: S
authors.lastname: Sambhara
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Mittal
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000367:Age Factors; D000818:Animals; D000075202:Contraindications; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000235:genetics / Q000276:immunology*
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D023083:beta-Defensins
keywords: Adenovirus vector-based vaccines; Aged mice; Immunostimulation; Influenza; Murine β-defensin 2; Vaccine for elderly
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