Vaccination to conserved influenza antigens in mice using a novel Simian adenovirus vector, PanAd3, derived from the bonobo Pan paniscus

PLoS One. 2013;8(3):e55435. doi: 10.1371/journal.pone.0055435. Epub 2013 Mar 11.

Abstract

Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines.

MeSH terms

  • Adenoviruses, Human / immunology
  • Adenoviruses, Simian / genetics
  • Adenoviruses, Simian / immunology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Cross Reactions / immunology
  • Female
  • Gene Expression
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Genetic Vectors / immunology*
  • Humans
  • Immunity, Mucosal
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / immunology*
  • Mice
  • Molecular Sequence Data
  • Nucleocapsid Proteins
  • Nucleophosmin
  • Orthomyxoviridae Infections / prevention & control*
  • Pan paniscus
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology
  • Viral Matrix Proteins / chemistry
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • NP protein, Influenza A virus
  • NPM1 protein, human
  • Npm1 protein, mouse
  • Nucleocapsid Proteins
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Viral Core Proteins
  • Viral Matrix Proteins
  • Nucleophosmin

Grant support

Research funding was provided by Okairòs and by CBER, FDA. Authors from Okairòs are employees of and/or shareholders in Okairòs, which is developing vectored vaccines for malaria and other diseases. All decisions concerning study design, data collection and analysis, decision to publish, and preparation of the manuscript were those of the authors, with concurrence of all authors.