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

• Published in: Virus research Vol. 178; no. 2; pp. 398 - 403
• Main Authors: Vemula, Sai V., Amen, Omar, Katz, Jacqueline M., Donis, Ruben, Sambhara, Suryaprakash, Mittal, Suresh K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 26-12-2013
• 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; Asia; Africa; Avian influenza; Murine beta-defensin 2; Adenovirus; Pandemic influenza vaccine; Influenza; Adenovirus vector-based vaccines
• ISSN: 0168-1702; 1872-7492
• DOI: 10.1016/j.virusres.2013.09.013

•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.