ABSTRACT
The capsid of foot-and-mouth disease virus (FMDV) displays several independent B cell epitopes, which stimulate the production of neutralising antibodies. Some of these epitopes are highly variable between virus strains, but dominate the immune response. The site A on VP1 is the most prominent example of a dominant and variable site. This variability is a problem when designing vaccines against this disease, because it necessitates a close match between vaccine strain and virus in an outbreak. We have introduced a series of mutations into viral capsid proteins with the aim of selectively silencing two dominant and highly variable epitopes and thereby divert immune responses toward less dominant but more conserved, protective epitopes. When mice were immunized with modified antigens, the resulting immune responses showed a higher degree of cross-reactivity towards heterologous virus as compared to mice vaccinated with wild type epitopes. Most of the modifications did not adversely affect the ability of the plasmids to induce complete protection of mice against homologous challenge.
Subject(s)
Capsid Proteins/immunology , Foot-and-Mouth Disease Virus/immunology , Foot-and-Mouth Disease/immunology , Foot-and-Mouth Disease/prevention & control , Immunodominant Epitopes/immunology , Plasmids/genetics , Viral Vaccines/immunology , Animals , Antigens, Viral/genetics , Antigens, Viral/immunology , Capsid Proteins/genetics , Epitopes, B-Lymphocyte/genetics , Epitopes, B-Lymphocyte/immunology , Foot-and-Mouth Disease Virus/genetics , Immunodominant Epitopes/genetics , Mice , Vaccines, DNA/genetics , Vaccines, DNA/immunology , Viral Vaccines/genetics , ViremiaABSTRACT
Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs are potent stimulators of the innate immune system, and are capable of aborting several infections in a non-specific manner. We here report studies of the capacity of such ODN to protect mice against infection with foot and mouth disease virus (FMDV). Susceptibility of Balb/c mice to infection with isolates from the different serotypes of FMDV was investigated, and, at the same time, the capacity of CpG ODN to modulate the infection was evaluated. Treatment with CpG significantly reduced viremia, disease and death in five of six serotypes, when compared to no treatment or treatment with a control ODN. The effect was observed when ODN was administered simultaneously with, or up to 12h after, infection with FMDV, and lasted for 14 days post treatment. The potential application of CpG ODN for control of FMDV during an outbreak is discussed.
Subject(s)
CpG Islands , Foot-and-Mouth Disease Virus , Foot-and-Mouth Disease/prevention & control , Immunization , Oligonucleotides/administration & dosage , Animals , Dose-Response Relationship, Drug , Female , Foot-and-Mouth Disease/pathology , Foot-and-Mouth Disease/virology , Foot-and-Mouth Disease Virus/classification , Injections, Subcutaneous , Mice , Mice, Inbred BALB C , Oligonucleotides/genetics , Serotyping , ViremiaABSTRACT
Porcine circovirus type 2 (PCV2) is the causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome (PMWS). The disease affects primarily 5-12-weeks-old pigs which might suggest that infection with PCV2 occurs when the level of maternal antibodies have declined to sub-protective levels around weaning at 3-5-weeks of age. If immunoprophylaxis is to be effective, an immunisation method capable of breaking through maternal immunity must be employed. In this study, we have developed and investigated the potential of a DNA vaccination approach to be one such method. The gene encoding the capsid protein of PCV2 was cloned in a DNA vaccination plasmid and expression of capsid protein was demonstrated in vitro. Mice were gene gun vaccinated three timesand all mice responded serologically by raising antibodies against PCV2. The results suggest, that DNA based vaccination might offer opportunities for vaccination of piglets against PCV2.