Characterization of live influenza vaccine donor strain derived from cold-adaptation of X-31 virus.
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 degrees C followed by 24 degrees 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 degrees 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.
Lee
Kwang-Hee
KH
Department of Biotechnology, College of Engineering, Yonsei University, 134 Shinchon-Dong, Sodaemun-Gu, Seoul 120-749, South Korea.
Seo
Sang-Uk
SU
Song
Jae-Min
JM
Lee
Chung-Min
CM
Kim
Hyun-Ah
HA
Seong
Baik L
BL
D000222:Adaptation, Physiological; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D001835:Body Weight; D002460:Cell Line; D002642:Chick Embryo; D003080:Cold Temperature; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053121:Influenza A Virus, H2N2 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D010641:Phenotype; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D010948:Viral Plaque Assay
D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated