TY - JOUR

T1 - Live attenuated influenza vaccines against highly pathogenic H5N1avian influenza

T2 - Development and preclinical characterization

AU - Larionova, Natalie

AU - Kiseleva, Irina

AU - Isakova-Sivak, Irina

AU - Rekstin, Andrey

AU - Dubrovina, Irina

AU - Bazhenova, Ekaterina

AU - Ross, Ted M.

AU - Swayne, David

AU - Gubareva, Larisa

AU - Tsvetnitsky, Vadim

AU - Fedorova, Ekaterina

AU - Doroshenko, Elena

AU - Rudenko, Larisa

PY - 2013/12

Y1 - 2013/12

N2 - In this paper we describe the development and the outcomes of the preclinical studies of temperature-sensitive and cold-adapted candidates for live attenuated influenza vaccine (LAIV) based on highly pathogenic avian influenza viruses A/H5N1 with pandemic potential. The LAIV candidates were developed by methods of classical reassortment between H2N2 Master Donor Virus for Russian LAIV and H5N1 viruses generated by reverse genetics for inactivated vaccine. These reverse genetically generated viruses were chosen as a source of H5 hemagglutinin and contained a modified protease cleavage site believed to be associated with high virulence. The progeny of reassortment had 7:1 gene composition and were characterized by antigen specificity of the HA of the pandemic virus, a high growth rate in chicken embryos and their parameters of temperature sensitivity and cold adaptation confirmed preserved attenuation of the Master Donor Virus. In addition, one H5N1 LAIV 6:2 reassortant was generated by reverse genetics. When tested in appropriate animal models, all candidates for H5N2 LAIV vaccine were found to be safe, immunogenic and effective in protecting from severe disease, mortality and pathology caused by the homologues lethal challenge virus and they almost completely eliminated challenge virus replication in vaccinated animals. They did not appear to differ in tested properties from the reverse genetically generated H5N1 LAIV 6:2 reassortant which contained wild-type N1-neuraminidase in addition to H5-hemagglutinin. The most promising for further clinical trials has been considered a LAIV candidate to virus A/turkey/Turkey/1/2005 (H5N1, clade 2.2).

AB - In this paper we describe the development and the outcomes of the preclinical studies of temperature-sensitive and cold-adapted candidates for live attenuated influenza vaccine (LAIV) based on highly pathogenic avian influenza viruses A/H5N1 with pandemic potential. The LAIV candidates were developed by methods of classical reassortment between H2N2 Master Donor Virus for Russian LAIV and H5N1 viruses generated by reverse genetics for inactivated vaccine. These reverse genetically generated viruses were chosen as a source of H5 hemagglutinin and contained a modified protease cleavage site believed to be associated with high virulence. The progeny of reassortment had 7:1 gene composition and were characterized by antigen specificity of the HA of the pandemic virus, a high growth rate in chicken embryos and their parameters of temperature sensitivity and cold adaptation confirmed preserved attenuation of the Master Donor Virus. In addition, one H5N1 LAIV 6:2 reassortant was generated by reverse genetics. When tested in appropriate animal models, all candidates for H5N2 LAIV vaccine were found to be safe, immunogenic and effective in protecting from severe disease, mortality and pathology caused by the homologues lethal challenge virus and they almost completely eliminated challenge virus replication in vaccinated animals. They did not appear to differ in tested properties from the reverse genetically generated H5N1 LAIV 6:2 reassortant which contained wild-type N1-neuraminidase in addition to H5-hemagglutinin. The most promising for further clinical trials has been considered a LAIV candidate to virus A/turkey/Turkey/1/2005 (H5N1, clade 2.2).

KW - Attenuated

KW - Cold-adapted phenotype

KW - Highly pathogenic avian influenza virus

KW - Live attenuated influenza vaccine

KW - Master donor virus

KW - Potential pandemic vaccines

KW - Temperature sensitive

UR - http://www.scopus.com/inward/record.url?scp=84892147674&partnerID=8YFLogxK

U2 - 10.4172/2157-7560.1000208

DO - 10.4172/2157-7560.1000208

M3 - Article

AN - SCOPUS:84892147674

VL - 4

JO - Journal of Vaccines and Vaccination

JF - Journal of Vaccines and Vaccination

SN - 2157-7560

IS - 8

M1 - 208

ER -