Development of adenoviral-vector-based pandemic influenza vaccine against antigenically distinct human H5N1 strains in mice

Lancet. 2006 Feb 11;367(9509):475-81. doi: 10.1016/S0140-6736(06)68076-8.

Abstract

Introduction: Avian H5N1 influenza viruses currently circulating in southeast Asia could potentially cause the next pandemic. However, currently licensed human vaccines are subtype-specific and do not protect against these H5N1 viruses. We aimed to develop an influenza vaccine and assessed its immunogenicity and efficacy to confer protection in BALB/c mice.

Methods: We developed an egg-independent strategy to combat the avian influenza virus, because the virus is highly lethal to chickens and the maintenance of a constant supply of embryonated eggs would be difficult in a pandemic. We used a replication-incompetent, human adenoviral-vector-based, haemagglutinin subtype 5 influenza vaccine (HAd-H5HA), which induces both humoral and cell-mediated immune responses against avian H5N1 influenza viruses isolated from people.

Findings: Immunisation of mice with HAd-H5HA provided effective protection from H5N1 disease, death, and primary viral replication (p<0.0001) against antigenically distinct strains of H5N1 influenza viruses. Unlike the recombinant H5HA vaccine, which is based on a traditional subunit vaccine approach, HAd-H5HA vaccine induced a three-fold to eight-fold increase in HA-518-epitope-specific interferon-gamma-secreting CD8 T cells (p=0.01).

Interpretation: Our findings highlight the potential of an Ad-vector-based delivery system, which is both egg-independent and adjuvant-independent and offers stockpiling options for the development of a pandemic influenza vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Birds
  • Humans
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / isolation & purification
  • Influenza A Virus, H5N1 Subtype / physiology
  • Influenza Vaccines / immunology
  • Influenza Vaccines / therapeutic use*
  • Influenza in Birds / immunology
  • Influenza in Birds / prevention & control*
  • Influenza in Birds / transmission
  • Influenza, Human / immunology
  • Influenza, Human / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / prevention & control*
  • Virus Replication / drug effects
  • Virus Replication / immunology

Substances

  • Influenza Vaccines