Research in Veterinary Science /986, 40, 303-307 Foot-and-mouth disease vaccination: a multifactorial study of the influence of antigen dose and potentially competitive immunogens on the response of cattle of different ages L. BLACK*, M. J. NICHOLLSt, M. M. RWEYEMAMU:j:, Welfcome Foot-and-Mouth Disease Vaccine Laboratory, Pirbright, Surrey, GU240NQ, R. FERRARI, M. A. ZUNINO, Cooper Uruguay Ltd, Casilla de Correo 569, Montevideo, Uruguay Groups of 68 and 66 cattle aged 12 and 24 months respectively were each subdivided into 16 groups and inoculated with foot-and-mouth disease vaccines con- taining 0. Campos, A 24 Cruzeiro and C 3 Pando virus strains. The 140S antigen mass of the 0 1 and A 24 valencies was varied while that of C 3 was held constant. Multifactorial comparisons between the 21 day serum neutralising antibody titres showed that over most of the range there was a linear log dose response relationship. Doubling the antigen dose increased the serum antibody titres against both A 24 Cruzeiro and 0 1 Campos by approximately 0·15 loglo' The A 24 antigen was about 30 times more immunogenic than the 0 1 with C 3 intermediate between the two. At high antigen doses the responses flattened but the level at which this occurred depended on the immunogen administered. No dif- ference could be demonstrated between the responses of 12- and 24-month-old cattle and there was no evidence of competitive inhibition or enhancement between the virus strains included in the vaccines. PREVIOUS results have shown that the virus neutral- ising antibody (VN50) responses of cattle were a linear function of the 140S antigen dose (loglQ) after inoculation of foot-and-mouth disease (FMD) vaccines containing O,BFS 1860 strain (Rweyemamu et al 1984, Black et al 1984). However, before regarding the antigen mass as a valid indication of vaccine potency it is necessary to evaluate the activity of other variables which may influence the responses. Past reports have shown that FMD strains differ in immunogenicity (Guinet et al 1982, Morgado et al 1982) and in the work described here the response to 'Present address: Hamshere Cottage, The Street, Wonersh, Surrey GU50PF tPresent address: c/o FCO (Dhaka, Bangladesh), King Charles Street, London SWIA 2AH, UK :j:Present address: Pfizer SA, via Presidente Dutra km 225, Caixa Postal 143, 07000-Guarulhos, Sao Paulo, Brazil strains selected from three commonly occurring sero- types (0, A and C) have been examined. In addition, the possibility that the different immunogens might exert either an inhibitory (Abramoff et al 1961, Cremer 1963) or comple- mentary effect, one on the other, was also investi- gated. This is of importance because most commercial FMD vaccines are multivalent and previous investiga- tions on competitive inhibition have usually evaluated the responses at only a single dose level for each antigen. Jerne (1967), however, pointed out that competition phenomena are likely to be dose dependent. In the studies reported here the doses of two FMD strains were varied widely, while that of the third was held constant. Previously unvaccinated cattle 12 and 24 months old, derived from vaccinated mothers, were used in these experiments because although young cattle are capable of producing effective antibody responses (Shankar and Uppal 1982, Nicholls et al 1985) these can be inhibited by the presence of low titres of maternal antibody at the time of vaccination (Nicholls 1983, Nicholls et at 1984). The analyses were confined to the 21-day responses since this corresponds to the interval employed in FMD vaccine potency tests. The effect of the 140S antigen mass on the time response profiles are to be included in a separate publication. Materials and methods Animals One hundred and thirty-four Hereford crossbred steers and heifers were used. Sixty-eight were approx- imately 12 months old and sixty-six were approx- imately 24 months old. The animals were kept under ranching conditions on a farm near Montevideo, Uruguay. They were born from and suckled on dams which had been vaccinated at regular four-month intervals although they themselves had never been previously vaccinated against FMD. 303