Attempt to modify the immune response developed against FIV gp120 protein by preliminary FIV DNA injection A.M. Cuisinier *, A. Meyer, B. Chatrenet, A.S. Verdier, A. Aubert Virbac Laboratories, BP 27, 06511 Carros Cedex, France Received 13 October 1997; received in revised form 18 May 1998; accepted 26 May 1998 Abstract Following inactivated virus vaccination trials, the surface glycoprotein gp120 (SU) of the feline immunode®ciency 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 in¯uence 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 g IFN mRNA signal after challenge speci®c for the p10 nucleocapsid and recSU proteins. However, no NC speci®c 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 modi®ed and that recombinant proteins could be a component of an eective vaccine. # 1999 Elsevier Science Ltd. All rights reserved. Keywords: Vaccine; DNA immunization; FIV 1. Introduction Feline immunode®ciency virus (FIV) causes in dom- estic cat pathogenesis analogous to that of HIV induced human AIDS [2, 37]. The humoral and cellular immune responses as well as target cells, evolution of infection and level of virus expression are similar in FIV and HIV infections. Cats infected by FIV rep- resent then an excellent animal model for studying immune responses developed against lentiviruses caus- ing immunode®ciency. In order to study the major protective antigens, vaccination trials were carried out. Vaccination experiments with inactivated virus and whole cell vaccines based on the FL4 cell line achieved protection [19, 23, 38, 51, 52]. Consequently, the surface glycoprotein (SU) was considered as one of the deter- minants for protection [22] by inducing high virus neutralizing antibodies (VNA) and a strong cross- reactive cytolysis (Yamamoto et al. unpublished results). However, subunit vaccines, especially Env subunit vaccines, failed to induce protection and, on the contrary, certain formulations facilitated viral dissemination [16, 20, 22, 23, 28, 34, 45, 48]. These exper- iments suggest that recombinant Env protein, despite the addition of adjuvants stimulating the cellular immune response, preferentially induces a TH2-like re- sponse by stimulating a dominant humoral response which favors viral replication. The result of vacci- nations depends on the choice of the adjuvant. The recSU protein mixed with an adjuvant favoring the TH2 pathway induces facilitation. Contrarily, the Vaccine 17 (1999) 415±425 0264-410X/99/$19.00 # 1999 Elsevier Science Ltd. All rights reserved. PII: S0264-410X(98)00212-6 * Corresponding author. Tel.: +33-4-92087545; fax: +33-4-92087199.