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

Article

关键词: AVIAN INFLUENZA;    MF59-ADJUVANTED INFLUENZA;    RECOMBINANT ADENOVIRUS;    REVERSE GENETICS;    IMMUNOGENICITY;    SAFETY;    VIRUS;    PROTECTION;    CELLS;    RESPONSES;   

DOI  :  10.1016/S0140-6736(06)68076-8

来源: SCIE

【 摘 要 】

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 art 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.

【 授权许可】

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