Cell-cultured, live attenuated, X-31ca-based H5N1 pre-pandemic influenza vaccine.
The manufacture of influenza vaccines has traditionally depended upon a method using embryonated hen's eggs. However, concerns regarding the potential shortage of the influenza substrate in the event of a pandemic has led to the development of cell culture-derived vaccines, which offers shorter lead-in times and greater production flexibility. We examined optimal conditions for the production of reassortant X-31ca-based H5N1 cold-adapted live attenuated influenza vaccine (rH5N1ca) cultured in mammalian cell lines. During ten passages in MDCK cells, the rH5N1ca vaccine maintained cold-adapted and temperature-sensitive phenotypes, and no mutations occurred in the hemagglutinin and neuraminidase surface antigens, demonstrating genetic and phenotypic stability. Single immunization in mice with the rH5N1ca induced robust antibody responses and protected the mice against lethal challenge. Stable maintenance of attenuation phenotypes and immunogenicity of the rH5N1ca from cell-culture suggest that they can be produced as a stockpile for pandemic preparedness as an alternative to current egg-based production.
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
Yun Ha
YH
Lee
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
Yo Han
YH
Jang
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea; Vaccine Translational Research Center, Yonsei University, Seoul, South Korea. Electronic address: blseong@yonsei.ac.kr.
Baik Lin
BL
Seong
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004285:Dogs; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009439:Neuraminidase / Q000235:genetics / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D058873:Pandemics / Q000517:prevention & control; D064166:Vaccine Potency; D014613:Vaccines, Attenuated / Q000276:immunology*; D014709:Vero Cells
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D009439:Neuraminidase
Cell culture; HPAI H5N1; Influenza virus; Live vaccine