Long-term vaccine-induced heterologous protection against H5N1 influenza viruses in the ferret model.
BACKGROUND
Highly pathogenic H5N1 influenza viruses reemerged in humans in 2003 and have caused fatal human infections in Asia and Africa as well as ongoing outbreaks in poultry. These viruses have evolved substantially and are now so antigenically varied that a single vaccine antigen may not protect against all circulating strains. Nevertheless, studies have shown that substantial cross-reactivity can be achieved with H5N1 vaccines. These studies have not, however, addressed the issue of duration of such cross-reactive protection.


OBJECTIVE
To directly address this using the ferret model, we used two recommended World Health Organization H5N1 vaccine seed strains - A/Vietnam/1203/04 (clade 1) and A/duck/Hunan/795/02 (clade 2.1) - seven single, double, or triple mutant viruses based on A/Vietnam/1203/04, and the ancestral viruses A and D, selected from sequences at nodes of the hemagglutinin and neuraminidase gene phylogenies to represent antigenically diverse progeny H5N1 subclades as vaccine antigens.


RESULTS
All inactivated whole-virus vaccines provided full protection against morbidity and mortality in ferrets challenged with the highly pathogenic H5N1 strain A/Vietnam/1203/04 5 months and 1 year after immunization.


CONCLUSIONS
If an H5N1 pandemic was to arise, and with the hypothesis that one can extrapolate the results from three doses of a whole-virion vaccine in ferrets to the available split vaccines for use in humans, the population could be efficiently immunized with currently available H5N1 vaccines, while the homologous vaccine is under production.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN, USA.
Mariette F
MF
Ducatez
Ashley
A
Webb
Jeri-Carol
JC
Crumpton
Richard J
RJ
Webby
D000818:Animals; D001831:Body Temperature; D001835:Body Weight; D056738:Cross Protection; D004195:Disease Models, Animal; D005289:Ferrets; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D009296:Nasal Cavity / Q000821:virology; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D016019:Survival Analysis; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D019562:Viral Load
D007252:Influenza Vaccines; D015164:Vaccines, Inactivated