British freeze-dried BCG vaccine: Further clinical trials

Abstract

Three batches of freeze-dried BCG vaccine with different viable cell counts have been studied and one of them compared with Danish liquid vaccine in a series of controlled trials in healthy, newborn infants. Freeze-dried vaccine (Batch 50) with a viable count of 0·10–0·14 × 10 6 /ml. produced very small vaccination lesions without any complications but tuberculin conversion was sub-optimal. The vaccine was considered too weak for general use. Freeze-dried vaccine (Batch 77) with a viable count of 23–31 × 10 6 /ml. produced vaccination papules of too large a size with frequent ulceration. There was significant enlargement of axillary or infraclavicular lymph nodes in 10 per cent of the infants. Tuberculin conversion was adequate. The vaccine is considered too strong for routine use. The third batch of freeze-dried vaccine (Batch 93a) was chosen with a viable cell count of 10–11 × 10 6 /ml. It produced moderate-sized papules (average diameter 10·3 mm.); and significant axillary lymph-node enlargement developed in 2·5 per cent of 158 infants given this batch. It was compared concurrently with Danish liquid vaccine which produced papules 9·3 mm. in diameter (average); 4 per cent of 173 infants developed significant lymph-node enlargement. Mantoux tuberculin conversion (100 TU) six to eleven weeks after vaccination with freeze-dried vaccine Batch 93a and with the Danish liquid vaccine were virtually the same, being 100 per cent. With 10 TU both vaccines gave just under 50 per cent conversion. With these two vaccines Mantoux tuberculin tests were also carried out using 10 TU of tuberculin (PPD) prepared from BCG. The incidence of positive reactions was the same as with 100 TU of Old Tuberculin, i.e. almost 100 per cent. The vaccines were five to ten months old when vaccinations were commenced with them. No evidence of deterioration was seen during the trial when the vaccines were stored at room temperature, nor was there any fall in the viable cell count during subsequent storage at 4°C. for fifteen to twenty-four months after preparation. The results of the one-year follow-up of babies injected with vaccines tested in a previous trial are presented. It is concluded that a freeze-dried vaccine with a viable count of 10 × 10 6 /ml. (1 × 10 6 viable cells/dose) is suitable for use both in contacts and for mass vaccination purposes. Stronger vaccines which produce big lesions are undesirable. It is probable that a weaker vaccine might still be satisfactory (e.g. 5 × 10 6 viable cells/ml.); further trials are planned to test vaccines of this potency.