Cross-protection against lethal H5N1 challenge in ferrets with an adjuvanted pandemic influenza vaccine.
BACKGROUND
Unprecedented spread between birds and mammals of highly pathogenic avian influenza viruses (HPAI) of the H5N1 subtype has resulted in hundreds of human infections with a high fatality rate. This has highlighted the urgent need for the development of H5N1 vaccines that can be produced rapidly and in sufficient quantities. Potential pandemic inactivated vaccines will ideally induce substantial intra-subtypic cross-protection in humans to warrant the option of use, either prior to or just after the start of a pandemic outbreak. In the present study, we evaluated a split H5N1 A/H5N1/Vietnam/1194/04, clade 1 candidate vaccine, adjuvanted with a proprietary oil-in- water emulsion based Adjuvant System proven to be well-tolerated and highly immunogenic in the human (Leroux-Roels et al. (2007) The Lancet 370:580-589), for its ability to induce intra-subtypic cross-protection against clade 2 H5N1/A/Indonesia/5/05 challenge in ferrets.


RESULTS
All ferrets in control groups receiving non-adjuvanted vaccine or adjuvant alone failed to develop specific or cross-reactive neutralizing antibodies and all died or had to be euthanized within four days of virus challenge. Two doses of adjuvanted split H5N1 vaccine containing >or=1.7 microg HA induced neutralizing antibodies in the majority of ferrets to both clade 1 (17/23 (74%) responders) and clade 2 viruses (14/23 (61%) responders), and 96% (22/23) of vaccinees survived the lethal challenge. Furthermore lung virus loads and viral shedding in the upper respiratory tract were reduced in vaccinated animals relative to controls suggesting that vaccination might also confer a reduced risk of viral transmission.


CONCLUSIONS
These protection data in a stringent challenge model in association with an excellent clinical profile highlight the potential of this adjuvanted H5N1 candidate vaccine as an effective tool in pandemic preparedness.
Baras
Benoît
B
Preclinical Virology, GlaxoSmithKline Biologicals, Rixensart, Belgium.
Stittelaar
Koert J
KJ
Simon
James H
JH
Thoolen
Robert J M M
RJ
Mossman
Sally P
SP
Pistoor
Frank H M
FH
van Amerongen
Geert
G
Wettendorff
Martine A
MA
Hanon
Emmanuel
E
Osterhaus
Albert D M E
AD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005289:Ferrets; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014779:Virus Replication
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines