Enhancement of the efficacy of a replication-defective adenovirus-vectored vaccine by the addition of oil adjuvants.

Abstract

We previously constructed a recombinant adenovirus with a defective E1A 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 concentrations (10(8) TCID50 per dose) of the virus were used and it gave mice little protection. The combination of the recombinant adenovirus 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, oil-in-water, water-in-oil-in-water) led to an increase in specific antibody responses and protection for the host when challenged with a virulent pseudorabies virus under very severe conditions, i.e. where 100% of unvaccinated mice died. A water-in-oil-in-water formulation induced a very high level of anti-gp50 antibodies even with a low concentration of adenovirus. These results could be correlated to the induction of cytokines, such as IL6, which is observed with this galenic form. The oil-adjuvanted emulsions induced IL2, suggesting that they were able 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 different proteins.