The sequence corresponding to the B-cell epitope of VP1 from FMDV O1/Campos/Bra/58 (140C158) comprises the amino acid residues = 2) were challenged at the same time, and the same procedure was followed

The sequence corresponding to the B-cell epitope of VP1 from FMDV O1/Campos/Bra/58 (140C158) comprises the amino acid residues = 2) were challenged at the same time, and the same procedure was followed. vaccine. For example, the vaccine provides short-term protection, resulting in the need for revaccination [1], and there is a risk of the GNE-495 infectious virus being released during vaccine GNE-495 production. Therefore, a number of countries with large livestock industries have abandoned vaccination. However, this policy leaves livestock herds prone to sudden outbreaks of FMD, with dramatic effects on livestock economy and animal welfare, as seen in the United Kingdom in 2001 [2, 3] and in turn has led to intensive research on alternative vaccination strategies. The FMD viral particle consists of a positive-strand RNA genome, a single open reading frame (ORF) which encodes four capsid proteins, VP1, VP2, VP3, and VP4, and eleven different mature nonstructural proteins (NSP). The B-cell binding site located in the G-H loop (around residues 140C160) of FMDV VP1 protein has been identified as a predominant epitope that elicits neutralizing antibodies against this virus in natural hosts and animal models [4, 5]. A T-cell epitope, located at residues 21 to 35 of FMDV NSP 3A, efficiently stimulates lymphocytes from pigs infected with a type C virus [6]. The current inactivated FMD vaccines only promote serological protection against a given FMDV serotype, do not confer interserotype protection, and may not, in some cases, confer intraserotype protection given the antigenic variation existing within some serotypes [7]. Additionally, these vaccines present other shortcomings, such as possible incomplete inactivation of virus, need for biosafety level 4 (BSL-4 OIE) laboratories, and requirement for a cold chain to preserve virus stability. On the other hand, the vaccine virus must be purified enough as not to induce detectable antibodies against viral NSP to allow a distinction between vaccinated and infected animals [8]. Peptide vaccines are an attractive alternative strategy that relies on the usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences [9]. Various synthetic peptide or recombinant protein vaccines based on the FMDV VP1 G-H loop have been shown effective in pigs [10C12], but they have shown limited efficacy in cattle [13C15], pointing to the limitations of these vaccines in eliciting broad protective responses in different hosts. Synthetic peptides are particularly attractive FMDV vaccine candidates as they are highly pure, defined, stable, and safe, and due to their modular approach, they can incorporate different B- and T-cell peptides [9, 16]. Multiple antigenic peptides (MAPs) are dendrimeric (branched) macromolecules built from a lysine core from which a defined number of epitopes radiate [17, 18]. An effective peptide vaccine needs a B-cell epitope to elicit a high neutralizing antibody response and a T-cell epitope to provide adequate GNE-495 cooperation between T-cells and B-lymphocytes. The dendrimeric peptide design improves the effectiveness of viral antigenic site presentation to the immune system. Recent studies indicate that vaccination with dendrimeric peptides based on the amino acid sequence of 3A (T-cell epitope) and VP1 GH loop (B-cell epitope) from the type O FMDV O/UKG/11/2001, and branched by means of thioether or maleimide conjugation chemistries, elicits an immune response that achieved protection in up to 100% of the vaccinated pigs [16]. Likewise, we recently reported that similar dendrimeric peptides, based on the amino acid sequences from the type O FMDV O1/Campos/Bra/58, including a Mouse monoclonal to HDAC4 VP4 sequence as T-cell epitope, can protect cattle against homologous challenge [19]. The aim of this study was to investigate whether dendrimeric peptides elicited protection against heterologous viruses, a relevant issue for efficient vaccine design. To this end, the immune response elicited in cattle by dendrimers containing amino acid sequences of 3A and VP1 GH loop from type O FMDV O/UKG/11/2001, B2T and B4T, and the protection they afforded against the heterologous type O virus O1/Campos/Bra/58, was analyzed. Our results indicate that B2T and B4T elicited specific humoral responses in cattle and conferred partial protection against the challenge with a heterologous virus O1/Campos/Bra/58..