Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics.
Bibliographical noteFunding Information:
This research was supported by the Vaccine Translational Research Center funded by the Ministry of Health and Welfare of Korean government (Grant No. HI13C0826 ) and also by the National Research Foundation of Korea (NRF) (Grant Nos. NRF2015R1D1A4A01016640 and NRF2014M3A9E4064743 ). The funding source did not have roles in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
All Science Journal Classification (ASJC) codes
- Molecular Medicine
- Immunology and Microbiology(all)
- Public Health, Environmental and Occupational Health
- Infectious Diseases