Studies on Cold Adapted Live Influenza Virus Vaccine Candidates

摘要

Derivation and characterization of cold recombinant clones with surface antigens to new epidemic strains (A/Texas-like-H3N2 and A/USSR-H1N1) have been accomplished. Clones with different gene composition were developed, plaque-purified and volunteers pool made for field trials, in order to evaluate the gene constellation necessary for cold-adaptation and hence, attenuation. The isolates derived from field trials this year provided evidence for stability of the cold-adapted (CA) marker only. In some isolates, CA marker was retained while reversion to ts+ was evident. These isolates were attenuated upon administration to ferrets. A new rapid enzymatic procedure is being developed for derivation of cold mutants. The advantage so far, has been the possibility of developing stable cold variants in about four weeks. Data obtained in comparative analysis of AA-CR29-Clone 2, in two host systems, MDCK and PCKC, showed differences in temperature cut-off. Two clones, picked at 39C from infected MDCK line and considered ts+, were still ts in primary chick kidney cells (PCKC). Host restriction should be considered when evaluating of marker(s) of candidates of influenza virus vaccine. Recently clones to AA-CR37 (A/California-H1N1) and AA-CR39 (A/Fukushima-H1N1) were picked and are being evaluated.