HIGH-YIELD PRODUCTION OF AN INACTIVATED COXSACKIE B3 ADJUVANT VACCINEWITH PROTECTIVE EFFECT AGAINST EXPERIMENTAL MYOCARDITIS

Dilated cardiomyopathy, perhaps chronic postviral fatigue syndrome as well as juvenile diabetes could be triggered by enteroviral infections . The frequency of sudden death after myocarditis and its relationship to enteroviral infections is disputed. Neonatal enteroviral disease i s rare, but can be severe. It is also possible that enteroviruses pose a threat to immunocompromised patients, like bone marrow transplant r ecipients. Consequently, the emergence of chronic enteroviral diseases as a concept, prompted our attempts to produce an enteroviral vaccine . 1. Live attenuated enterovirus strains were previously in some cases shown to be suitable as vaccine candidates. We obtained neutralizing antibody titres ranging from 40-2560 against Coxsackie B3 virus (RD st rain). Animals were protected to 90% against challenge infection. 2. I nactivated whole vaccine. We used beta-propiolactone to inactivate Cox sackie B3 virus. 74 % of the animals survived if the vaccine was prepa red with Quil A matrix as adjuvant. The neutralisation antibody titres varied from <5 to 320. By comparison aluminium hydroxide (p=0.06) and Freunds adjuvant were inferior (p<0.01). 3. Subunit vaccines. We have previously used the ISCOM (immuno stimulatory complex)technology to p roduce a Coxsackie B3 subunit vaccine. High levels of neutralizing ant ibodies were obtained (512) - comparable to natural Infection. All ani mals survived challenge infection after two booster doses with 16 nano gram of the ISCOM preparation. Limiting for this technique was the ava ilability to include sufficient amount of antigenic protein material. In addition to neutralizing antibodies a cellular response might be ob tainable. In conclusion we have shown that vaccine can be made against Coxsackie B3 virus with good protective effect and significant neutra lisation antibody titre. A high yield of vaccine antigen was obtained by inactivation with beta-propiolactone (no purification step) and goo d adjuvant effect was noted with Quil A matrix.