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


RESULTS
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).


CONCLUSIONS
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.
Hoelscher
Mary A
MA
Influenza Branch, Division of Rickettsial and Viral Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Garg
Sanjay
S
Bangari
Dinesh S
DS
Belser
Jessica A
JA
Lu
Xiuhua
X
Stephenson
Iain
I
Bright
Rick A
RA
Katz
Jacqueline M
JM
Mittal
Suresh K
SK
Sambhara
Suryaprakash
S
D000818:Animals; D001717:Birds; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
D007252:Influenza Vaccines