Vaccination of Infants with Living Attenuated Measles Vaccine (Edmonston Strain) with and without Gamma-globulin

Abstract

The first trials of measles vaccines in the United Kingdom were reported in 1961 by Aldous et al., when three living attenuated vaccines derived from the Edmonston strain (Enders et al., 1960) were compared at the Fountain Hospital. In many cases vaccination reactions were too pronounced for the vaccines to be suitable for routine use. However, in view of the high complication rate of measles in young children (Miller, 1964), it was considered important to continue clinical trials of measles vaccine rendered less toxic by further attenuation. The present paper describes four subsequent trials of vaccines prepared from the Edmonston strain but which had undergone a further series of passages in chick-embryo or chick-cell tissue cultures. In some of the trials the vaccines were given alone, and in others concurrently with gamma-globulin. Methods General PlanThe trials were carried out in healthy infants or young children with no previous history of measles. Four separate studies were made: in each of the first three, two vaccines were compared, and in the fourth one vaccine was tested. When two vaccines were compared the children were allocated at random to receive one or other vaccine. A serum sample was taken immediately before vaccination and a second sample four weeks after vaccination. Virus-neutralizing antibody titres were determined on the pre-and post-vaccination samples in parallel Vaccine 20: This strain was a descendant of Enders's Edmonston B primary seed virus, and had been subjected to a total of 77 additional chick-embryo tissue-culture passages at 33' C.The preparation and testing of vaccines 14, 16, and 20 followed the procedure described previously (Goffe and , modified by the inclusion of supplementary tests in embryonated eggs and chick-embryo tissue cultures. Thefinal vaccines were given a more extensive safety test in animals than had been used previously. The virus content of each batch was titrated in tissue culture, using HEp-2 cells, by the 50% cytopathic endpoint method. It was later checked by retitration of samples of the final vaccines, which were returned unused from some of the immunization sessions. The virus titres per human dose of the vaccine were as follows: vaccine 4a, 10"4 per ml.; vaccine 14, 10-32 per ml. ; vaccine 16, 1037 per ml. ; vaccine 20, 103.5 per ml.

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