Characterization of live influenza vaccine donor strain derived from cold-adaptation of X-31 virus

• Published in: Vaccine 2006-03, Vol.24 (11), p.1966-1974
• Main Authors: Lee, Kwang-Hee, Seo, Sang-Uk, Song, Jae-Min, Lee, Chung-Min, Kim, Hyun-Ah, Seong, Baik L.
• Format: Article
• Language: English
• Subjects: Adaptation, Physiological; Administration, Intranasal; Animals; Antibodies, Viral - blood; Applied microbiology; Attenuation; Biological and medical sciences; Body Weight; Cell Line; Chick Embryo; Cold Temperature; Dogs; Enzyme-Linked Immunosorbent Assay; Female; Fundamental and applied biological sciences. Psychology; Immunization; Immunogenicity; Infections; Influenza; Influenza A virus; Influenza A virus - genetics; Influenza A virus - growth & development; Influenza A virus - immunology; Influenza A virus - pathogenicity; Influenza A Virus, H2N2 Subtype - immunology; Influenza A Virus, H3N2 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Influenza virus; Live vaccine; Lung - virology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Neutralization Tests; Orthomyxoviridae Infections - prevention & control; Orthomyxoviridae Infections - virology; Pathogens; Phenotype; Temperature; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - adverse effects; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Viral Plaque Assay; Virology; Viruses
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.10.051

A human influenza A virus X-31 (high-yielding strain) was cold-adapted for possible future use as live attenuated vaccine. Mutant influenza viruses were selected during successive serial passage in embryonated hens’ eggs at progressively lower sub-optimal temperature (30, 27 °C followed by 24 °C). The cold-passaged mutant exhibited both temperature-sensitivity ( ts) and cold-adapted ( ca) phenotypes. The pathogenicity and immunogenicity of X-31 ca virus were studied in mice following intranasal inoculation. The mice did not show clinical signs even at high titer infection. Immunization of mice with X-31 ca virus elicited high titers of neutralizing antibody and provided complete protection against homologous and heterologous virus challenges. To assess the genetic stability, the X-31 ca virus was passaged at 37 °C in MDCK cells or inoculated into mice. Revertant virus was not found in the lungs of any of the mice and the supernatants of the MDCK culture. We conclude that the X-31 ca candidate vaccine virus exhibits the desired level of attenuation, immunogenicity, and protective efficacy required for live attenuated vaccine and merits further evaluation at clinical level.