ES417157A1 - Viral mutants and vaccines - Google Patents

Abstract

Procedure for obtaining and isolating dominant strains from a strain of influenza virus, capable of undergoing mutation leading to the formation of dominant strains, characterized by cycles of operations that each comprise the production of a serum homologous to the strain of the virus, determining the relative doses of this homologous serum that. can neutralize in vitro the normal development of a corresponding culture of the same virus, the production of n different and individual cultures of the aforementioned viruses in the presence of the homologous serum, the concentration initially used of the virus, in each of the individual cultures, being lower of the mutation frequency of the strain in question, the number n of cultures being large enough so that, on the one hand, the product of the aforementioned initial concentration of virus and the number n are at least equal to the mutation frequency of the cultured virus and, on the other hand, the probability of the formation of two mutants in the same culture is practically negligible, the dose of the homologous serum applied to each culture being greater than that necessary to produce said neutralization and chosen so that it is obtained without However, the development of 1 ap of said n cultures, p being an integer, a function of the frequency of mutation n mentioned, low enough with respect to n that the probability that the cultures that have grown can be considered mutants and, finally, the characterization of each of the 1 ap cultures having taken place, especially by comparison of the measured serum titers Test in hemagglutination inhibition assays with respect to the aforementioned 1 ap cultures as well as to the ancestor strains of the cultivated strain, the recovery as dominant mutants of those of the aforementioned 1 ap cultures having a reduced sensitivity with respect to the effect inhibitor of the reference sera, provided that the differences between these titers and those of the ancestor strains are greater than predetermined threshold values, said cycles being repeated in the "dominant mutants" thus obtained, more particularly in the less sensitive mutants of the cultures 1 ap isolated from the preceding cycle, said c being substantially repeated cycles until further development of strains significantly different from that applied in the cycle in question is obtained, in the presence of doses of the homologous serum such as those defined above. (Machine-translation by Google Translate, not legally binding)