Antigenic competition in a multivalent foot rot vaccine

Area of Science:

• Veterinary immunology
• Bacterial pathogenesis
• Vaccine development

Background:

• Foot rot in sheep is a significant economic issue caused by Dichelobacter nodosus.
• Pilus antigens are key targets for vaccines against Dichelobacter nodosus infections.
• Multivalent vaccines aim to provide broad protection but can suffer from antigenic competition.

Purpose of the Study:

• To investigate antigenic competition among Dichelobacter nodosus pilus antigens in a multivalent vaccine.
• To assess the impact of combining multiple pilus serogroups on antibody response and protective immunity in sheep.
• To elucidate the mechanisms underlying reduced efficacy in multivalent foot rot vaccines.

Main Methods:

• Development of a prototype multivalent vaccine using recombinant pilus antigens from nine Dichelobacter nodosus serogroups expressed in Pseudomonas aeruginosa.
• Vaccination of sheep with monovalent and multivalent vaccines.
• Measurement of agglutinating and total antibody levels specific for pilus antigens using ELISA and agglutination assays.
• Evaluation of protection against foot rot post-vaccination.
• Experiments involving varying antigen doses, administration routes, and monospecific sera.

Main Results:

• Sheep vaccinated with the multivalent vaccine exhibited significantly lower levels of specific antibodies (both agglutinating and total) compared to those receiving monovalent vaccines.
• The reduction in antibody levels was more pronounced for agglutinating antibodies, which are crucial for protection.
• Antigenic competition was observed even with high antigen loads and varied administration sites, indicating a complex immunological interaction.
• The phenomenon was unlikely due to blocking by cross-reactive non-protective antibodies.

Conclusions:

• Combining multiple Dichelobacter nodosus pilus serogroups in a multivalent vaccine leads to significant antigenic competition, diminishing the immune response and protective efficacy.
• The study highlights challenges in developing effective multivalent vaccines for foot rot due to complex antibody interactions.
• Further research is needed to overcome antigenic competition and improve the design of broad-spectrum foot rot vaccines.