Vaccination of mice with plasmids expressing processed capsid protein of foot-and-mouth disease virus--importance of dominant and subdominant epitopes for antigenicity and protection.
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.
Frimann
Tine Holland
TH
National Veterinary Institute, Technical University of Denmark, Lindholm, DK-4771 Kalvehave, Denmark.
Barfoed
Annette Malene
AM
Aasted
Bent
B
Kamstrup
Søren
S
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology; D005536:Foot-and-Mouth Disease / Q000276:immunology* / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010957:Plasmids / Q000235:genetics*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014766:Viremia
D000956:Antigens, Viral; D036022:Capsid Proteins; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; C442501:VP1 protein, Foot-and-mouth disease virus; C442459:VP2 protein, Foot-and-mouth disease virus; C442460:VP3 protein, Foot-and-mouth disease virus; D019444:Vaccines, DNA; D014765:Viral Vaccines