Enhanced Mucosal Immunoglobulin A Response and Solid Protection against Foot-and-Mouth Disease Virus Challenge Induced by a Novel Dendrimeric Peptide

Abstract

The successful use of a dendrimeric peptide to protect pigs against challenge with foot-and-mouth disease virus (FMDV), which causes the most devastating animal disease worldwide, is described. Animals were immunized intramuscularly with a peptide containing one copy of a FMDV T-cell epitope and branching out into four copies of a B-cell epitope. The four immunized pigs did not develop significant clinical signs upon FMDV challenge, neither systemic nor mucosal FMDV replication, nor was its transmission to contact control pigs observed. The dendrimeric construction specifically induced high titers of FMDV-neutralizing antibodies and activated FMDV-specific T cells. Interestingly, a potent anti-FMDV immunoglobulin A response (local and systemic) was observed, despite the parenteral administration of the peptide. On the other hand, peptideimmunized animals showed no antibodies specific of FMDV infection, which qualifies the peptide as a potential marker vaccine. Overall, the dendrimeric peptide used elicited an immune response comparable to that found for control FMDV-infected pigs that correlated with a solid protection against FMDV challenge. Dendrimeric designs of this type may hold substantial promise for peptide subunit vaccine development.

Foot-and-Mouth Disease Virus Can Induce a Specific and Rapid CD4+T-Cell-Independent Neutralizing and Isotype Class-Switched Antibody Response in Naïve Cattle

“…A general problem with most subunit vaccines is that they do not elicit a protective immune response comparable with that induced by live virus or killed whole-virus vaccines (66). Peptide vaccines based on the G-H loop (70) do not appear to fully mimic the conformation of the native B-cell epitopes and stimulate antibody of rather narrow specificity, which appears to be T-D (19,25,42). In contrast, studies of responses to traditional FMDV vaccines, which utilize intact inactivated virus, have shown that they stimulate rapid antibody responses that can provide protection against disease within 4 to 5 days.…”

Attenuated Foot-and-Mouth Disease Virus RNA Carrying a Deletion in the 3′ Noncoding Region Can Elicit Immunity in Swine

“…Induction of specific IgA responses was detected in serum from the animals showing a higher neutralizing response (pigs 4 and 8). Several studies associate the induction of specific IgA with protection and suggest that vaccines that induce local IgA responses may be more effective (18,22,26). Moreover, mutant transcripts were able to induce a specific T-cell response in four out of the eight animals inoculated.…”

“…upper mucosae has been correlated with protection in infected and vaccinated pigs (18,22,26). ELISA titers of Ͼ2 (corresponding to a 1:50 dilution of serum) were detected for both animals.…”

Infectious Diseases: Need for Targeted Drug Delivery

“…This is a combination of polymer-lipid containing doxycycline which could have application in the treatment of intracellular infections that are primarily resident in the spleen like brucellosis, ehrlichiosis, etc. A number of studies are reported on horses infected with babesiosis, Streptococcus equi, T. gondii and Strongylus vulgaris infections using liposomes [ 254 ], polymeric nanospheres [ 255 ], dendrimers [ 256 ] and micelles [ 257 ] respectively. A recent study revealed the improved therapy of theileiriosis in cattle with solid lipid nanoparticles (SLN) of buparvaquone [ 258 ].…”