No abstract

No abstract

No abstract

No abstract

Tick-borne encephalitis (TBE) virus, like many other arboviruses, is very stable in genetic characteristics such as neurovirulence. Extreme difficulty has been encountered in efforts to reduce its pathogenicity artificially and therefore many attempts in the U.S.S.R. to attenuate the virus and to develop a live vaccine for mass vaccination have been unsuccessful. A killed formol-vaccine has therefore been widely used since 1939 (Smorodintsev, Levkovich & Dankovsky, 1940;Smorodintsev et al. 1941), at first made in mouse brain and later in tissue culture (Smorodintsev & Ilyenko, 1961). Unfortunately such vaccines have to be given annually and a more effective and convenient live vaccine would be a considerable advantage if safe and immunogenic vaccine strains could be found.Our first step in this direction was the study of the Langat (TP 21 strain) virus (Smith, 1956) because of its close antigenic relationship to TBE and absence of known natural disease caused by it in humans in Malaya. The mouse-adapted variant of Langat virus can be sharply differentiated from typical TBE virus on the basis of its inability to infect mice by intraperitoneal (IP) or subcutaneous (SC) inoculation and rhesus monkeys by intracerebral (IC) injection. The original Malayan strain grows poorly in chick embryo cells (CEC) at 40°C. and does not grow at 41-50 C. The original mouse brain virus contains a mixture of strains more or less pathogenic for mice, monkeys and man. The proportion of more virulent virus in the original mouse brain virus is very small but increases very sharply after five or more passages in CEC. Using terminal dilutions (which cause less than 50 % mortality in mice infected IC) thirty-eight pure clones of Langat virus including two virulent and thirty-six avirulent variants have been isolated from mouse-brain virus. These two main types of variant were genetically stable and were not changed in virulence by prolonged passage at 360 or 400 C. in tissue culture or by prolonged mouse-brain passage.