Challenging settled opinions in classic foot-and-mouth disease vaccine preparation.

In a previous study we challenged the generally accepted opinion that inactivation of FMDV by formaldehyde (FA) is an (unsafe) non-linear process. Our data showed that under proper conditions inactivation will be linear without "tailing-off". For more than forty years two other fixed beliefs existed with respect to FMD vaccine preparation: Virus must first be adsorbed to Al(OH)3-gel before being inactivated. Concentrations of formaldehyde are critical and must be within a very narrow range. Until recently the prescription of adsorption of the virus prior to inactivation made proper control of inactivation kinetics impossible. However, by eluting the virus from the gel by caesium chloride density centrifugation, the kinetics of inactivation can be studied. For adsorbed and non-adsorbed virus, identical inactivation curves were found. Antigenicity was found to be of identical "quality" for adsorbed and non-adsorbed virus. The second dogma was challenged by inactivating non-adsorbed virus with FA-concentrations of up to 6 times the one originally prescribed. In parallel inactivation was performed with acetyl-ethylene-immine (AEI). The antigen was purified after inactivation. Antigen yields after purification were systematically lower at high FA-concentrations, however, antigenicity seemed only slightly changed by the treatments: In an immunosorbent (ELISA) assay using a panel of 22 monoclonal antibodies (McAb) only few McAb's reacted differently with FA-treated antigen if compared with AEI-treated or fresh (A10) FMDV. The FA-treatment induced decreases, as well as increases in reactivities. The AEI-treated virus reacted almost identically to non-treated 146S particles.(ABSTRACT TRUNCATED AT 250 WORDS)