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Characterization of reverse genetics-derived cold-adapted master donor virus A/Leningrad/134/17/57 (H2N2) and reassortants with H5N1 surface genes in a mouse model.
Clin Vaccine Immunol. 2014 May; 21(5):722-31.CV

Abstract

Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (wt) A/Leningrad/134/1957 and cold-adapted (ca) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV), we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) virus. A mouse model of infection was used to determine the infectivity and tissue tropism of the parental wt viruses compared to the ca master donor viruses as well as the H5N1 reassortants. All ca viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the ca MDV. Mice inoculated twice 4 weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum hemagglutination inhibition HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous wt H5N1 highly pathogenic avian influenza (HPAI) viruses. The profiles of viral replication in respiratory tissues and the immunogenicity and protective efficacy characteristics of the two ca H5N1 candidate LAIV viruses warrant further development into a vaccine for human use.

Authors+Show Affiliations

Influenza Division, Centers for Disease Control and Prevention, Department of Health and Human Services, Atlanta, Georgia, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24648485

Citation

Isakova-Sivak, Irina, et al. "Characterization of Reverse Genetics-derived Cold-adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants With H5N1 Surface Genes in a Mouse Model." Clinical and Vaccine Immunology : CVI, vol. 21, no. 5, 2014, pp. 722-31.
Isakova-Sivak I, Chen LM, Bourgeois M, et al. Characterization of reverse genetics-derived cold-adapted master donor virus A/Leningrad/134/17/57 (H2N2) and reassortants with H5N1 surface genes in a mouse model. Clin Vaccine Immunol. 2014;21(5):722-31.
Isakova-Sivak, I., Chen, L. M., Bourgeois, M., Matsuoka, Y., Voeten, J. T., Heldens, J. G., van den Bosch, H., Klimov, A., Rudenko, L., Cox, N. J., & Donis, R. O. (2014). Characterization of reverse genetics-derived cold-adapted master donor virus A/Leningrad/134/17/57 (H2N2) and reassortants with H5N1 surface genes in a mouse model. Clinical and Vaccine Immunology : CVI, 21(5), 722-31. https://doi.org/10.1128/CVI.00819-13
Isakova-Sivak I, et al. Characterization of Reverse Genetics-derived Cold-adapted Master Donor Virus A/Leningrad/134/17/57 (H2N2) and Reassortants With H5N1 Surface Genes in a Mouse Model. Clin Vaccine Immunol. 2014;21(5):722-31. PubMed PMID: 24648485.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of reverse genetics-derived cold-adapted master donor virus A/Leningrad/134/17/57 (H2N2) and reassortants with H5N1 surface genes in a mouse model. AU - Isakova-Sivak,Irina, AU - Chen,Li-Mei, AU - Bourgeois,Melissa, AU - Matsuoka,Yumiko, AU - Voeten,J Theo M, AU - Heldens,Jacco G M, AU - van den Bosch,Han, AU - Klimov,Alexander, AU - Rudenko,Larisa, AU - Cox,Nancy J, AU - Donis,Ruben O, Y1 - 2014/03/19/ PY - 2014/3/21/entrez PY - 2014/3/22/pubmed PY - 2014/12/23/medline SP - 722 EP - 31 JF - Clinical and vaccine immunology : CVI JO - Clin Vaccine Immunol VL - 21 IS - 5 N2 - Live attenuated influenza vaccines (LAIV) offer significant advantages over subunit or split inactivated vaccines to mitigate an eventual influenza pandemic, including simpler manufacturing processes and more cross-protective immune responses. Using an established reverse genetics (rg) system for wild-type (wt) A/Leningrad/134/1957 and cold-adapted (ca) A/Leningrad/134/17/1957 (Len17) master donor virus (MDV), we produced and characterized three rg H5N1 reassortant viruses carrying modified HA and intact NA genes from either A/Vietnam/1203/2004 (H5N1, VN1203, clade 1) or A/Egypt/321/2007 (H5N1, EG321, clade 2) virus. A mouse model of infection was used to determine the infectivity and tissue tropism of the parental wt viruses compared to the ca master donor viruses as well as the H5N1 reassortants. All ca viruses showed reduced replication in lungs and enhanced replication in nasal epithelium. In addition, the H5N1 HA and NA enhanced replication in lungs unless it was restricted by the internal genes of the ca MDV. Mice inoculated twice 4 weeks apart with the H5N1 reassortant LAIV candidate viruses developed serum hemagglutination inhibition HI and IgA antibody titers to the homologous and heterologous viruses consistent with protective immunity. These animals remained healthy after challenge inoculation with a lethal dose with homologous or heterologous wt H5N1 highly pathogenic avian influenza (HPAI) viruses. The profiles of viral replication in respiratory tissues and the immunogenicity and protective efficacy characteristics of the two ca H5N1 candidate LAIV viruses warrant further development into a vaccine for human use. SN - 1556-679X UR - https://www.unboundmedicine.com/medline/citation/24648485/Characterization_of_reverse_genetics_derived_cold_adapted_master_donor_virus_A/Leningrad/134/17/57__H2N2__and_reassortants_with_H5N1_surface_genes_in_a_mouse_model_ L2 - http://cvi.asm.org/cgi/pmidlookup?view=long&pmid=24648485 DB - PRIME DP - Unbound Medicine ER -