The dynamics of alterations in biological properties of A/PR/8/34 virus strain was studied in the process of prolonged adaptation to the growth in chick embryos (CE) at a lowered (25 degrees C) cultivation temperature. The variant selected after 59 passages and subsequent cloning at the above temperature retained the high reproductive capacity in CE at optimal temperature (34 degrees C) - a characteristic of the original strain. Unlike to the latter, it showed a distinctly reduced ability to reproduce at 40 degrees C and a lower level of pathogenicity for white mice and CE. Analysis of genes of the cloned cold-adapted A/PR/8/34 strain detected 5 ts mutations in genes 1, 3, 5, 6 and 7 coding for P3, P2, NP, NA and M proteins, respectively.
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The vaccine strains for live attenuated influenza vaccines (LAIVs) have cold-adapted, temperature-sensitive, and attenuated phenotypes, which are guaranteed by the presence of specific mutations from the master donor virus in their internal genes. In this study, we used mutant viruses of the pathogenic A/Puerto Rico/8/34 (H1N1) that contained ts-mutations in PB1 (K265N, V591I), PB2 (V478L), and PA (L28P, V341L) genes along and/or in different combinations to evaluate the impact of these mutations in the immune responses. Sequential addition of tested mutations resulted in the stepwise decrease in virus-specific serum and, to a lesser extent, mucosal antibody levels.
View Article and Find Full Text PDFPLoS One
September 2013
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, PR China.
Human influenza is a seasonal disease associated with significant morbidity and mortality. The most effective means for controlling infection and thereby reducing morbidity and mortality is vaccination with a three inactivated influenza virus strains mixture, or by intranasal administration of a group of three different live attenuated influenza vaccine strains. Comparing to the inactivated vaccine, the attenuated live viruses allow better elicitation of a long-lasting and broader immune (humoral and cellular) response that represents a naturally occurring transient infection.
View Article and Find Full Text PDFBMC Biotechnol
October 2012
Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstr 1, 39106 Magdeburg, Germany.
Background: Current influenza vaccines are trivalent or quadrivalent inactivated split or subunit vaccines administered intramuscularly, or live attenuated influenza vaccines (LAIV) adapted to replicate at temperatures below body temperature and administered intranasally. Both vaccines are considered safe and efficient, but due to differences in specific properties may complement each other to ensure reliable vaccine coverage. By now, licensed LAIV are produced in embryonated chicken eggs.
View Article and Find Full Text PDFReassortants of cold-adapted strain A/Leningrad/134/47/57 (H2N2) and virulent strain A/PR/8/34 (H1N1), modeling genomic composition of vaccinal strains, were tried in mouse experiments. Reassortants' genomes included the major part (5, 6, or 7) from cold-adapted strain and 1 to 3 genes of virulent strain. All the tested reassortants did not differ by temperature sensitivity or cold adaptation phenotypes, did not cause the death of mice, but differed by the level of reproduction in murine lungs and by immunogenicity.
View Article and Find Full Text PDFVaccine
January 1994
Department of Virology, Russian Academy of Medical Sciences, St Petersburg.
Interference between pairs of cold-adapted (ca) influenza A and B vaccine reassortant viruses and between ca influenza B reassortant viruses and wild-type influenza strain A/PR/8/34 was studied in embryonated eggs and/or in the respiratory tract of three strains of mice. Interference in eggs between ca A and B reassortants occurred after 2 days but was masked by later cycles of growth. When doses of 10(6) EID50 of the reassortant viruses B/60/32/R and A/47/6/R were administered to outbred mice, interference with the growth of A/47/6/R occurred in the turbinates; interference with the growth of B/60/32/R did not occur.
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