Clinical Trials of Oil-adjuvant Influenza Vaccines, 1960–3

Virus Vaccines* Brit.med.J., 1964, 2, 267-271 Influenza vaccine prepared by emulsifying an aqueous suspension of inactivated virus in mineral oil is a far more potent antigen than the aqueous suspension alone.This fact was confirmed by the Committee in serological trials carried out in 1953 (M.R.C., 1955), but subsequent large-scale clinical trials in 1954-5 failed to show any protective effect, almost certainly because there was very little influenza during that winter (M.R. C., 1957).Unfortunately a small proportion (3.0 per thousand) of the volunteers who received oil-adjuvant vaccine developed persistent local reactions, similar to those described in the United States by Philip et al. (1954).These reactions were usually first noticed as fibrotic nodules several months after inoculation and took a year or more to resolve.In about half the cases (1.8 per thousand) the nodules became large and fluctuant and cleared only after incision.In an attempt to overcome this problem, small-scale studies were made during 1956-8, using a different oil (Drakeol No. 6 instead of Bayol F), a more pure preparation of the emulsifier (Arlacel A) and vaccine of various viscosities (Himmelweit, 1960).The results of this work showed that vaccines of low viscosity gave as good an antibody response as those of higher viscosity, and it seemed possible that a low- viscosity vaccine might be less likely to produce a foreign-body reaction and subsequent necrosis.The number of subjects studied was too few, however, to allow any conclusions to be drawn on the risk of serious local reactions.Encouraged by the result of this work, a large field trial was begun in the autumn of 1960 in which over 6,000 adult volunteers were inoculated with low-viscosity vaccines by general practitioners, chest physicians, and industrial medical officers.The trial was continued for three winters, and its results are the subject of this report. Material and MethodsVaccines.-Twovaccines were used, one containing an egg- adapted influenza virus A2 strain (A2/Singapore/l/57) and the other an egg-adapted influenza virus B strain (B/England/939/ 59).Both vaccines were water-in-oil emulsions of low viscosity containing 2,000 haemagglutinating units of virus per dose (0.25 ml.); they were prepared by Dr. F. Himmeiweit at the Wright-Fleming Institute of Microbiology in the manner described previously (Himmelweit, 1960).Supplies of mineral oil (Drakeol No. 6) and of emulsifier (purified Arlacel A) were obtained from the United States through the courtesy of Dr. Fred M. Davenport, of the University of Michigan.The vaccines were dispensed in disposable cartridges each containing