Abstract
The emergence of a highly pathogenic avian influenza virus H5N1 has increased the potential for a new pandemic to occur. This event highlights the necessity for developing a new generation of influenza vaccines to counteract influenza disease. These vaccines must be manufactured for mass immunization of humans in a timely manner. Poultry should be included in this policy, since persistent infected flocks are the major source of avian influenza for human infections. Recombinant adenoviral vectored H5N1 vaccines are an attractive alternative to the currently licensed influenza vaccines. This class of vaccines induces a broadly protective immunity against antigenically distinct H5N1, can be manufactured rapidly, and may allow mass immunization of human and poultry. Recombinant adenoviral vectors derived from both human and non-human adenoviruses are currently being investigated and appear promising both in nonclinical and clinical studies. This review will highlight the current status of various adenoviral vectored H5N1 vaccines and will outline novel approaches for the future.
Highlights
Influenza is a contagious acute respiratory disease that remains a serious public-health problem today [1,2] and results in substantial economic burden every year [3], even though most influenza virus infections are self-limited
To mitigate the spread of this contagious virus and reduce the degree of pathogenicity in infected hosts, there is a critical need for an effective H5N1 pandemic preparedness plan [20], that likely requires a combination of pharmaceutical prophylaxis, treatment and non-pharmaceutical interventions
Hoelscher et al observed that mice intramuscularly or intranasally immunized with a recombinant adenoviral (rAd) expressing HA protein from A/Hong Kong/156/97 were effectively protected against lethal challenges with the heterologous (A/Hong Kong/483/97) and (A/Vietnam/1203/04) H5N1 influenza viruses, even without a strong humoral neutralizing response against A/Vietnam/1203/04 virus [119]
Summary
Influenza is a contagious acute respiratory disease that remains a serious public-health problem today [1,2] and results in substantial economic burden every year [3], even though most influenza virus infections are self-limited. Circulating highly pathogenic avian influenza (HPAI) H5N1 virus poses another potential pandemic threat to humans [10]. This virus emerged in 1996 and the first confirmed direct transmission of AIV to humans without an intermediate host was in 1997 during a poultry outbreak in Hong Kong [11,12]. H5N1 virus strains have spread from Asia to Europe and Africa and has caused severe disease in poultry and wild birds in multiple countries [13] These viruses crossed the species barriers infecting mammals, including domestic cats, Owston’s civets, leopards, tigers, dogs, stone martens, pigs, plateau pika, and humans [13]. Human transmissible HPAI H5N1 virus has the potential of being utilized as a bioterrorist weapon [19]
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