Attempt to modify the immune response developed against FIV gp120 protein by preliminary FIV DNA injection

Abstract

Following inactivated virus vaccination trials, the surface glycoprotein gp120 (SU) of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some Env-derived peptides failed to induce protection. To study the influence of the environment in which the surface protein (SU) is injected, we analyzed the impact of a nucleocapsid (NC) DNA immunization on the presentation of the recSU protein to the immune system. Cats were vaccinated either with the recSU protein alone or with NC DNA followed by the recSU protein. Two routes of nucleocapsid DNA vaccination were tested: intramuscular and mucosal injections. Cats immunized with the recSU protein showed a facilitation of infection, since they presented the earliest and the highest humoral response correlating with the highest proviral load. They also showed an acceleration of the appearance of IL4 mRNA signal. Preliminary injection of the DNA coding for NC protein, regardless the route of inoculation, seemed to inhibit the facilitation induced by vaccination with the recSU protein alone. The previously nucleocapsid DNA immunized cats had infectious status similar to those of the control cats, but with lower proviral load and less developed anti-FIV humoral response. Cat No. 2, belonging to the group vaccinated with NC protein by the mucosal route, had a protected-like status which did not correlate with the humoral response. This cat was the only one to have a persisting γ IFN mRNA signal after challenge specific for the p10 nucleocapsid and recSU proteins. However, no NC specific cytotoxic cells were observed throughout the experiment in this cat. The role of nucleocapsid DNA vaccination is still unknown nevertheless we did demonstrate that the facilitation observed in vaccination trial with recombinant proteins could be modified and that recombinant proteins could be a component of an effective vaccine.