Evaluation of Feline Monocyte-Derived Dendritic Cells Loaded with Internally Inactivated Virus as a Vaccine against Feline Immunodeficiency Virus

Abstract

Dendritic cells are the only antigen-presenting cells that can present exogenous antigens to both helper and cytolytic T cells and prime Th1-type or Th2-type cellular immune responses. Given their unique immune functions, dendritic cells are considered attractive "live adjuvants" for vaccination and immunotherapy against cancer and infectious diseases. The present study was carried out to assess whether the reinjection of autologous monocyte-derived dendritic cells loaded with an aldithriol-2-inactivated primary isolate of feline immune deficiency virus (FIV) was able to elicit protective immune responses against the homologous virus in naive cats. Vaccine efficacy was assessed by monitoring immune responses and, finally, by challenge with the homologous virus of vaccinated, mock-vaccinated, and healthy cats. The outcome of challenge was followed by measuring cellular and antibody responses and viral and proviral loads and quantitating FIV by isolation and a count of CD4 ؉ /CD8 ؉ T cells in blood. Vaccinated animals exhibited clearly evident FIV-specific peripheral blood mononuclear cell proliferation and antibody titers in response to immunization; however, they became infected with the challenge virus at rates comparable to those of control animals.

Utilizing the FIV model to understand dendritic cell dysfunction and the potential role of dendritic cell immunization in HIV infection

“…Several studies have shown that human monocyte-derived DC infected with HIV have reduced ability to stimulate allogeneic and mitogen-stimulated lymphocyte proliferation in vitro (Macatonia et al, 1989; Knight et al, 1993; Knight et al, 1997; Fantuzzi et al, 2004; Granelli-Piperno et al, 2004; Shan et al, 2007). In contrast to our studies, Freer et al (2008) showed that in vitro infection of monocyte-derived DC with a clade A FIV-petaluma virus did not impair subsequent lymphocyte proliferation. Conflicting study results may be due to the viral strain used, DC source, or differences in duration of infection and warrants further investigation.…”

“…Reggeti et al (2008) found that immunization of cats with allogeneic BM-derived DC did not induce cross-protective immunity against FIV that had been propagated in the same cells in vitro . Freer et al (2008) evaluated the potential of feline monocyte-derived DC loaded with AT-2-inactivated virus to provide protective immunity. DC were generated from peripheral blood mononuclear cells cultured in autologous plasma with GM-CSF and IL-4, loaded with AT-2-inactivated FIV, and matured with LPS.…”

“…Freer et al (2008) used monocyte-derived DC as a potential immunotherapy in chronic FIV infection. Feline monocyte-derived DC loaded with AT-2-inactivated homologous FIV, and matured with LPS, were shown to have high MHC class II and B7.1 expression and to stimulate MLRs as is characteristic of mature, functional DC.…”

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

“…In particular, the repeated inoculation of paraformaldehyde-fixed FIV-infected MBM cells afforded marked protection (43)(44)(45)69). However, the use of similarly fixed FIV-infected autologous infected T lymphocytes or of viable dendritic cells loaded with inactivated FIV failed to protect or even aggravated homologous virus challenge (18,21), thus excluding the possibility that the key to the success of the approach tested here was merely the use of a cellular boost. The reasons for its efficacy may be several that are not mutually exclusive.…”

“…Peripheral blood CD4 and CD8 T lymphocytes were counted as previously described (18). Briefly, 30 l of heparinized blood was incubated with 3 l of anti-feline CD4-or CD8-phycoerythrin (clones vpg34 and vpg9, respectively; AbD Serotec, Raleigh, NC) on ice for 30 min.…”