ENHANCEMENT OF THE EFFICACY OF A REPLICATION-DEFECTIVE ADENOVIRUS-VECTORED VACCINE BY THE ADDITION OF OIL ADJUVANTS

We previously constructed a recombinant adenovirus with a defective E1 A gene, which expresses high levels of the pseudorabies virus gp50 in non-transcomplementing cells. The virus is unable to replicate in mice . It elicited the production of anti-gp50 antibodies only when high co ncentrations (10(8) TCID50 per dose) of the virus were used and it gav e mice little protection. The combination of the recombinant adenoviru s at several concentrations (10(8), 10(7.4), 10(6.4) TCID50 per dose) with certain oil adjuvants in different galenic forms (water-in-oil, o il-in-water, water-in-oil-in-water) led to an increase in specific ant ibody responses and protection for the host when challenged with a vir ulent pseudorabies virus under very severe conditions, i.e. where 100% of unvaccinated mice died. A water-in-oil-in-water formulation induce d a very high level of anti-gp50 antibodies even with a low concentrat ion of adenovirus. These results could be correlated to the induction of cytokines, such as IL6, which is observed with this galenic form. T he oil-adjuvanted emulsions induced IL2, suggesting that they were abl e to activate T-helper cells. Different oil formulations elicited the different IgG subclasses (IgG1, IgG2a, IgG2b, IgG3). These results can be extended to other live replication-defective vaccines expressing d ifferent proteins.