Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential.
We generated a high-growth 7:1 reassortant (Len17/H5) that contained the hemagglutinin (HA) gene from non-pathogenic A/Duck/Potsdam/1402-6/86 (H5N2) virus and other genes from the cold-adapted (ca) attenuated A/Leningrad/134/17/57 (H2H2) strain. Len17/H5 demonstrated an attenuated phenotype in mice and did not infect chickens. Mice administered Len17/H5 either as a live-attenuated intranasal vaccine or as an inactivated intramuscular vaccine were substantially protected from lethal challenge with highly pathogenic A/Hong Kong/483/97 (H5N1) virus and were protected from pulmonary infection with antigenically distinct A/Hong Kong/213/2003 (H5N1) virus. The cross-protective effect correlated with the levels of virus-specific mucosal IgA and/or serum IgG antibodies. Our results suggest a new strategy of using classical genetic reassortment between a high-growth ca H2N2 strain and antigenically related non-pathogenic avian viruses to prepare live-attenuated and inactivated vaccines for influenza pandemic.
Desheva
J A
JA
Department of Virology, Institute of Experimental Medicine, RAMS, St Petersburg, Russia.
Lu
X H
XH
Rekstin
A R
AR
Rudenko
L G
LG
Swayne
D E
DE
Cox
N J
NJ
Katz
J M
JM
Klimov
A I
AI
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D002645:Chickens / Q000276:immunology*; D003429:Cross Reactions; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D007114:Immunization; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000472:pathogenicity; D053125:Influenza A Virus, H5N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology* / Q000517:prevention & control*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology; D014779:Virus Replication
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated