Development and characterization of cold-adapted viruses for use as live virus vaccines

Abstract

Representative viruses from twelve RNA and two DNA virus genera have been successfully adapted to growth at sub-optimal temperature (cold-adapted). In almost every case, there was a correlation between acquisition of the cold-adaptation phenotype and loss of virulence in the normal host whether animal or man. Overall, the best method of cold adaptation to develop a live virus vaccine line appeared to be a stepwise lowering of the growth temperature allowing time for multiple lesions to occur and/or be selected. In addition, the starting virus should be a recent isolate not as yet adapted to a tissue culture host and the cold-adaptation process should then occur in a host heterologous to the virus' normal host. These viruses have been reviewed in the light of their cold-adaptation method and successful production of an attenuated line as virus vaccine candidate. Finally, detailed information is presented for the cold-adaptation process in influenza virus.

Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets

“…The wt H6 viruses did not exhibit the ca phenotype; in each case, the replication of the wt virus at 25°C was reduced by more than 1,000-fold compared to the replication of the same virus at 33°C. As expected, the H6 ca viruses expressed the ca phenotype; the titer of each virus at 25°C was within 100-fold of its titer at 33°C (6,26). Thus, the three H6 ca viruses displayed the expected ts and ca phenotypes.…”

History of vaccination

“…enabled the creation of three major vaccines: live and inactivated influenza (26,27), as well as one of the two rotavirus vaccines (28). In the case of inactivated influenza, the objective is to select the segments coding for hemagglutinin and neuraminidase and to combine them with segments coding for the internal genes of viruses that grow well.…”

Molecular studies of influenza B virus in the reverse genetics era

“…Indeed studies in ferrets argue strongly for the use of a LAIV vaccine for influenza B virus rather than reliance on inactivated vaccine (Huber et al, 2008). Vaccine strains using B/Ann Arbor/1/66 as the master donor virus (MDV-B) display temperature sensitivity (ts), attenuation (att) and cold adaptation (ca) (Maassab & DeBorde, 1985) and are genetically stable (Snyder et al, 1989). These strains were initially created 2 4 2 3 4 3 6 0 3 2 4 2 9 5 8 9 4 4 2 9 3 3 3 5 9 4 5 4 5 6 0 2 3 1 0 1 6 1 9 4 5 3 7 1 0 3 7 2 5 2 4 2 0 9 0 8 2 6 4 3 2 6 3 0 through serial passages of the wild-type virus in embryonated chicken eggs and primary chicken kidney (PCK) cells at incrementally lower temperatures (Maassab, 1967).…”