Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens

Mol Ther. 2014 Mar;22(3):668-674. doi: 10.1038/mt.2013.284. Epub 2013 Dec 30.

Abstract

Adenoviruses are potent vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same drawbacks. We have constructed a replication-deficient chimpanzee adenovirus-vectored vaccine expressing the conserved influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1). Here, we report safety and T-cell immunogenicity following vaccination with this novel recombinant simian adenovirus, ChAdOx1 NP+M1, in a first in human dose-escalation study using a 3+3 study design, followed by boosting with modified vaccinia virus Ankara expressing the same antigens in some volunteers. We demonstrate ChAdOx1 NP+M1 to be safe and immunogenic. ChAdOx1 is a promising vaccine vector that could be used to deliver vaccine antigens where strong cellular immune responses are required for protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Simian / genetics*
  • Adolescent
  • Adult
  • Animals
  • Antigens, Viral / immunology
  • Dose-Response Relationship, Immunologic
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / adverse effects
  • HEK293 Cells
  • Humans
  • Influenza A virus / metabolism*
  • Influenza Vaccines / administration & dosage
  • Influenza Vaccines / adverse effects*
  • Influenza Vaccines / immunology
  • Middle Aged
  • Pan troglodytes / virology*
  • RNA-Binding Proteins / immunology
  • RNA-Binding Proteins / metabolism*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism
  • Vaccination / adverse effects
  • Viral Core Proteins / immunology
  • Viral Core Proteins / metabolism*
  • Viral Matrix Proteins / immunology
  • Viral Matrix Proteins / metabolism*
  • Virus Replication / immunology*
  • Young Adult

Substances

  • Antigens, Viral
  • Influenza Vaccines
  • M1 protein, Influenza A virus
  • NP protein, Influenza A virus
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Viral Core Proteins
  • Viral Matrix Proteins