Beta-defensin 2 enhances immunogenicity and protection of an adenovirus-based H5N1 influenza vaccine at an early time

•Mbd2 enhances Ad vaccine-induced immune response early post vaccination.•Mbd2 immunostimulation confers protection against H5N1 by day 7 post vaccination.•This vaccine strategy has implications for pandemic influenza preparedness. Reports of human infections with highly pathogenic H5N1 avian influe...

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Bibliographic Details
Published in:Virus research 2013-12, Vol.178 (2), p.398-403
Main Authors: Vemula, Sai V., Amen, Omar, Katz, Jacqueline M., Donis, Ruben, Sambhara, Suryaprakash, Mittal, Suresh K.
Format: Article
Language:English
Subjects:
Adenovirus
Adenovirus vector-based vaccines
Adenoviruses, Human - genetics
Adjuvants, Immunologic - administration & dosage
Animals
Antibodies, Viral - blood
antigen-presenting cells
Avian influenza
beta-Defensins - administration & dosage
cell-mediated immunity
Disease Models, Animal
epithelial cells
Female
Genetic Vectors
Hemagglutinin Glycoproteins, Influenza Virus - genetics
Hemagglutinin Glycoproteins, Influenza Virus - immunology
hemagglutinins
Human adenovirus
human diseases
humans
immune response
Influenza
Influenza A virus
Influenza A Virus, H5N1 Subtype - genetics
Influenza A Virus, H5N1 Subtype - immunology
Influenza Vaccines - administration & dosage
Influenza Vaccines - immunology
Influenza virus
Leukocytes, Mononuclear - immunology
Mice
Mice, Inbred BALB C
molecular weight
mortality
Murine beta-defensin 2
nucleoproteins
Orthomyxoviridae Infections - prevention & control
pandemic
Pandemic influenza vaccine
RNA-Binding Proteins - genetics
RNA-Binding Proteins - immunology
vaccination
Vaccination - methods
vaccines
Vaccines, Synthetic - administration & dosage
Vaccines, Synthetic - immunology
Viral Core Proteins - genetics
Viral Core Proteins - immunology
viruses
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Summary:•Mbd2 enhances Ad vaccine-induced immune response early post vaccination.•Mbd2 immunostimulation confers protection against H5N1 by day 7 post vaccination.•This vaccine strategy has implications for pandemic influenza preparedness. 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 (2×107+1×107) 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.
ISSN:0168-1702
1872-7492
DOI:10.1016/j.virusres.2013.09.013