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Title: CHARACTERIZATION OF AN INFLUENZA A H5N2 REASSORTANT AS A CANDIDATE FOR LIVE-ATTENUATED AND INACTIVATED VACCINES AGAINST HIGHLY PATHOGENIC H5N1 VIRUSES WITH PANDEMIC POTENTIAL

Author
item DESHEVA, J - ST PETERSBURG, RUSSIA
item LU, X - CDC - ATLANTA, GA
item REKSTIN, A - ST PETERBURG, RUSSIA
item RUDENKO, L - ST PETERSBURG, RUSSIA
item Swayne, David
item COX, N - CDC - ATLANTA, GA
item KATZ, J - CDC - ATLANTA, GA
item KLIMOV, A - CDC - ATLANTA, GA

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/14/2006
Publication Date: 11/17/2006
Citation: Desheva, J.A., Lu, X.H., Rekstin, A.R., Rudenko, L.G., Swayne, D.E., Cox, N.J., Katz, J.M., Klimov, A.I. 2006. Characterization of an influenza a H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential. Vaccine. 24(47-48):6859-6866.

Interpretive Summary: An effective human vaccine against the Asian H5N1 high pathogenicity avian influenza (HPAI) virus is not available. Through biotechnology, this study produced an H5N2 vaccine by using genes from low pathogenicity avian influenza virus and a cold adapted human influenza virus. The resulting vaccine was attenuated for a mouse model and did not infect chickens. Furthermore, the vaccine protected the mice from lethal challenge by Asian H5N1 HPAI virus. This vaccine has potential use in humans should an H5 pandemic occur in humans.

Technical Abstract: We generated a high-growth 7:1 reassortant (Len17/H5) that contained the hemagglutinin 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.