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.
Bibliographical noteFunding Information:
This study was supported by a grant of the Korea Health R&D Project (01-PJ1-PG4-01PT01-0024) from the Ministry of Health and Welfare and the Strategic Research Grant on the Control of Bioterror Agents (M1-01KG-01-0001) from the Ministry of Science and Technology, Republic of Korea.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Immunology and Microbiology(all)
- Public Health, Environmental and Occupational Health
- Infectious Diseases