Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time.
Reports of human infections with highly pathogenic H5N1 avian influenza viruses in many countries in Asia and Africa with varying case fatality rates highlight the pandemic potential of these viruses. In order to contain a rapidly spreading influenza virus in a pandemic scenario, a vaccine which can induce rapid and robust immune responses, preferably in a single dose, is necessary. Murine beta-defensin 2 (Mbd2), a small molecular weight protein expressed by epithelial cells, has been shown to enhance antigen-specific immune responses by recruiting and activating professional antigen presenting cells to the site of vaccination. This study assessed the potential of Mbd2 to enhance the immunogenicity and protective efficacy of a human adenovirus (HAd)-based vaccine expressing the hemagglutinin (HA) and nucleoprotein (NP) [HAd-HA-NP] of an H5N1 influenza virus. A single inoculation of mice with both HAd-HA-NP and a HAd vector expressing Murine β-defensin 2 (HAd-Mbd2) resulted in significantly higher levels of both humoral and cell-mediated immune responses compared to the groups vaccinated only with HAd-HA-NP. These responses were evident even at day 7 post-immunization. Furthermore, the HAd-HA-NP+HAd-Mbd2-immunized group receiving the lowest vector dose (2 × 10(7)+1 × 10(7)) was completely protected against an rgH5N1 virus challenge on day 7 post-vaccination. These results highlight the potential of Mbd2 as a genetic adjuvant in inducing rapid and robust immune responses to a HAd-based vaccine.
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; Bindley Bioscience Center, Purdue University, West Lafayette, IN, USA.
Sai V
SV
Vemula
Omar
O
Amen
Jacqueline M
JM
Katz
Ruben
R
Donis
Suryaprakash
S
Sambhara
Suresh K
SK
Mittal
D000260:Adenoviruses, Human / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D005822:Genetic Vectors; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D014611:Vaccination / Q000379:methods*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D023083:beta-Defensins / Q000008:administration & dosage*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D023083:beta-Defensins
Adenovirus; Adenovirus vector-based vaccines; Avian influenza; Influenza; Murine beta-defensin 2; Pandemic influenza vaccine