Conditions for proper formaldehyde inactivation of foot and mouse disease alhydrogel vaccines.

The inactivation of FMDV by formaldehyde (FA) was studied under different conditions, both as free virus and (as in routine vaccine production) after adsorption of the virus to aluminium hydroxide gel (alhydrogel). In the latter case infectivity was monitored after elution of the virus from the gel by isopycnic ultracentrifugation of the virus-alhydrogel mixture in CsCl. By this method good virus recoveries were obtained. Adsorption of the virus to alhydrogel (without formaldehyde) did not reduce infectivity significantly. Both adsorbed and non-absorbed virus lost infectivity at a rate of about one log10 per day (at pH 8.5, 25 degrees C - no formaldehyde). Kinetics of FA inactivation of adsorbed and non-adsorbed virus were also identical, with a fast reduction in the initial phase. After this initial phase inactivation became linear and rather slow. No 'tailing-off' was observed. Some additives (f.i. LAH and especially Tris) reduced the inactivation rate. These findings might explain some data of others who observed 'tailing-off'.