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Tests on bovines vaccinated 3 or 4 times against foot-and-mouth disease with vaccines based on viruses cultivated on BKH cells, in roller bottles, have allowed to define the nature of some of the principal allergens: on the one hand residuary horse serum used to saturate the filters employed in preparing the virus intended for the manufacture of vaccines and, on the other hand, the substances liberated by the cytopathogenic action of the virus on the BHK cells. The horse serum is the most active and causes general and local reactions which are sometimes severe. It is therefore replaced by calf serum intended to reduce the importance of the problem for bovines. BHK antigens (BHK extracts and virus) produce only local reactions which are generally less severe.

Nine strains of foot-and-mouth disease virus type "O" received in our laboratories since 1971 have been studied serologically by Osler's quantitative method of complement fixation (50% hemolysis). The results, submitted to the biomathematical system of bidimensional classification, allow to conclude that at present in Europe there are two groups of foot-and-mouth disease strains of type "O"; one has reference to our vaccinal strain "O Lausanne 1965" and the other to "O Romania 1972" strain, which has certain points of similarity with subtype "O2". In addition, strain "O Hungary 1975" has been studied on bovines; the immunological tests confirm the serological test.

The report compares the compatibility, efficacity and serology response of two bivalent anti-foot-and-mouth disease vaccines (OC). One is oil-adjuvanted and the other based on diethyl-amino-ethyl-dextran (DEAE-Dextran). After vaccination no general clinical or local reactions are normally observed. Tissular reactions at the inoculation site are more severe with the oil-adjuvanted vaccine than with the DEAE-Dextran vaccine. Meat inspection, about three months after injection of the vaccine, showed the lesions to be in regression and negligible. The control of activity has been performed by the virulence test. For the oil-adjuvanted vaccine, protection against O1-Lausanne, 5, 21 and 90 days after vaccination is 90%, 80-100% and 55% respectively. For the DEAE-Dextran vaccine, these levels of protection are 80% after 5 days and 20-70% after 21 days. The percentage of swine protected against C-Noville 35 days after vaccination is 100% for the oil-adjuvanted vaccine and 70% for the DEAE-Dextran vaccine. The evolution of the amount of serum antibodies was followed for three months by the method of seroneutralization on cell cultures.

The results obtained with Brucella B19 strain, used as adjuvant and stimulant in the preparation of hyperimmune anti-foot-and-mouth disease serums on guinea pigs, have led the authors to carry out a series of experiments with a combined anti-foot-and-mouth disease and anti-brucellosis vaccine (strain B 19 Buck and Cotton). The search for neutralizing antibodies for foot-and-mouth disease has been undertaken by different methods. In the search for antibrucellic antibodies reactions such as seroagglutination, fixation of the complement, etc. have been used. The results obtained with combined vaccine are identical with those obtained with each of the monovalent vaccines.

Medical and sanitary prevention of a growing number of major infectious diseases of bovines has led IFFA-Mérieux to investigate the association of vaccines and to define methods of utilization. Care has been taken to limit the number of interventions and at the same time to retain in the combined valences the efficacy they had when in a state of single constituent. The work which has been carried out for the last ten years, including the study of adjuvants as well as of incompatibility of associations, has permitted the improvement of formulas, reduced in volume (5 ml for a plurivalent dose), in aqueous excipient (aluminum hydroxide and saponin) or oily excipient (oil in water type). These formulas combine 3 foot-and-mouth disease valences with a rabies valence (fixed strain grown on cell culture) or with a brucellosis valence (strain B. abortus MacEwen 45/20 and B. melitensis H 38). The innocuity of these associations allows them to be used in sanitary compaigns; their efficacy is equal to that of monovalent vaccines. A logical vaccination calendar is proposed.

Two methods of evaluating the activity of the foot-and-mouth disease vaccine are compared, leading to the evaluation of the number of protective doses 50% or potency. These methods differ in sensitivity, precision and equivalence potency-percentage of protection. For the same vaccine the value of the PD50 is always larger than that of Pb. We chose the Pb method using a diluent containing no adjuvant. Standards based on the evaluation of average potency have not been taken into consideration; only those standards based on the evaluation of minimum potency ensure respect of OIE's recommendation. This recommendation: 70% minimum potency with 0.95 probability is not an easier alternative, since the average protection observed corresponds in fact to at least 90% taking into account the biological variability of bovines.

The study of the plaques produced by viruses Asia and O1 reveals different properties which may depend on the virus or on the cell or its method of culture. Antigenic differences and subsequent immunological differences correspond to differences in plaques. On the other hand, the cell line in suspension evolves both in its morphology and its receptivity during the passages. All these variations imply the observations of quantitative and qualitative criteria of evaluation in order to prepare vaccines from viruses similar to viruses specific to a given epizooty.

Innocuity testing in bovines remains the reference method but other methods using mice and especially cell cultures may be employed. Different techniques (dialysis, neutralization, elution, etc.) allow the elimination of toxic constituents of the vaccine while respecting the eventual presence of small quantities of active virus. The sensitivity of the cell cultures is certainly equal if not superior to that of the tongue of bovines. Interference phenomena do not intervene and, furthermore, there is not reason to fear them solely on cell cultures. From the purely statistical standpoint, it is hardly possible to prove the innocuity of a vaccine but the credit which sould be accorded to the innocuity test can be reinforced by a good control of the inactivation process and, a posteriori, by the repetition of negative results.

The characteristics of the viruses produced from cell lines developed in suspension and the vaccines for which they are used should be judged by methods which allow to ensure in all cases their innocuity and efficacity. Innocuity is essentially dependent upon the purity of the viral preparation which should contain a minimum of foreign proteins (due either to the cell or the culture medium) and certain antibiotics. Furthermore, the absence of oncogenic properties of the inactivated viral suspensions should be shown, in addition to their specific innocuity. Efficacity is linked with the concentration of viral particles and with their immunogenic properties after inactivation and incorporation of adjuvants of immunity. Methods of appreciation of the different parameters are proposed.

A certain number of parameters involved in the manufacture, control and use of an efficacious vaccine against foot-and-mouth disease have been studied. This report considers the problems raised by the standardization of the raw material constituent to the vaccine as well as the different types of innocuity and activity testing carried out on sows, young pigs and bacon pigs. Special attention is given to virulence testing methods, to the criteria allowing evaluation of the quality of the vaccines and to the transmission of maternal immunity of the sows to their piglets and its incidence on the vaccination schedule.

L'etude serologique et immunologique de la souche A Gafarsa, isolee en Ethiopie au cours de l'epizootie de 1974, montre qu'elle est differente des souches A isolees lors des precedentes epizooties. La couverture immunologique procuree par deux vaccins exotiques s'avere insuffisante pour proteger les bovins contre la souche A Gafarsa. (Resume d'auteur)

The ponderal quantity of 140 S antigens and their peptide distribution are controlled in concentrated virulent and inactivated preparations proir to their being transformed into vaccines. A certain variability in the amount of 140 S particles and in the titer of peptide sensitive to trypsin (VP1) has been demonstrated in the virulent preparations. After treatment by inactivating agents (glycidaldehyde, binary ethyleneimine and formaldehyde) two types of alteration of the viral capsid are shown : one leads to the partial cleavage of VP1 (glycidaldehyde and binary ethyleneimine), the other leads to the detaching of an important quantity of VP1 from the capsid (formaldehyde). The degradation by formadehyde of the 140 S particles of type O and type C into 12 S particles is underlined, as well as the relatuve stability of type A and the relatuve lability of type C. The results are discussed in terms of immunogenicity.