Immune Response and Partial Protection against Heterologous Foot-and-Mouth Disease Virus Induced by Dendrimer Peptides in Cattle.

Synthetic peptides mimicking protective B- and T-cell epitopes are good candidates for safer, more effective FMD vaccines. Nevertheless, previous studies of immunization with linear peptides showed that they failed to induce solid protection in cattle. Dendrimeric peptides displaying two or four copies of a peptide corresponding to the B-cell epitope VP1 [136-154] of type O FMDV (O/UKG/11/2001) linked through thioether bonds to a single copy of the T-cell epitope 3A [21-35] (termed B2T and B4T, resp.) afforded protection in vaccinated pigs. In this work, we show that dendrimeric peptides B2T and B4T can elicit specific humoral responses in cattle and confer partial protection against the challenge with a heterologous type O virus (O1/Campos/Bra/58). This protective response correlated with the induction of specific T-cells as well as with an anamnestic antibody response upon virus challenge, as shown by the detection of virus-specific antibody-secreting cells (ASC) in lymphoid tissues distal from the inoculation point.

Co-inoculation of baculovirus and FMDV vaccine in mice, elicits very early protection against foot and mouth disease virus without interfering with long lasting immunity.

Baculoviruses (Bvs) potentiate the immune response against soluble antigens. We investigated whether Bv could be used as immunoactivator in foot-and-mouth disease (FMD) vaccines using the BALB/c mouse model. Mice were vaccinated with a single dose of inactivated FMDV (iFMDV), iFMDV+Bv, Bv, or culture medium. Humoral and cellular immune responses were higher in animals immunized with iFMDV+Bv than in mice vaccinated with iFMDV alone. Animals receiving iFMDV+Bv had significantly lower viremia at 2, 4 and 7dpv, than those immunized with iFMDV alone. In order to prolong the immune response, iFMDV oil vaccine was co-inoculated with Bv. Animals receiving iFMDV oil vaccine+Bv were protected two days earlier than those receiving the iFMDV oil vaccine alone. Both formulations protected until 14dpv, the last day of the experiment. This is the first report in which Bv is used as an adjuvant in a FMDV vaccine.

Foot-and-mouth disease virus causes a decrease in spleen dendritic cells and the early release of IFN-α in the plasma of mice. Differences between infectious and inactivated virus.

Foot-and-mouth disease (FMD) is a highly contagious and acute viral disease of cloven-hoofed animals. From an economical point of view, it is the most important disease of livestock worldwide. It is known that the virus interacts with dendritic cells, both in the natural host and in mice, but the impact of this interaction on the adaptive immune response is controversial. Currently available vaccines are based on inactivated forms of the FMD virus. Little is known about the differences between infectious and inactivated virus, in terms of dendritic cell subsets involved in immune response activation. The present work, which was carried out in the murine model, shows that live virus infection induces a reduction in splenic dendritic cell subsets. In addition, lymphocyte proliferation is inhibited in the early stages of infection associated with IFN-α induction, but is restored to normal values 5 days post-infection when pro-inflammatory cytokines was produced. In contrast, the inactivated virus increases the percentage of plasmacytoid dendritic cells in the spleen and the production of IL-10, which triggers the activation of a T regulatory response.