Der p 1 peptide on virus-like particles is safe and highly immunogenic in healthy adults

Background: In mice, highly repetitive antigens, such as those present on bacterial or viral surfaces, efficiently cross-link B-cell receptors and therefore induce strong IgG responses. In this study we covalently coupled a synthetic 16-amino-acid sequence of the allergen Der p 1 to a virus-like particle derived from the bacteriophage Q beta (Q beta-Der p 1). Objective: We evaluated the safety and immunogenicity of Q beta-Der p 1 in human subjects and compared different doses and routes of immunization. Methods: In a phase I trial 24 healthy volunteers were randomly assigned to one of 4 treatment groups. Group I received 50 mu g of Q beta-Der p 1 intramuscularly, group 2 received 50 mu g of Q beta-Der p 1 subcutaneously, group 3 received 10 mu g of Q beta-Der p 1 intramuscularly, and group 4 received 10 mu g of Q beta-Der p 1 subcutaneously. Boosting immunizations with 10 jig were given after 1 and 3 months. Antibody titers were measured after 1, 3, 4, 6, 12, and 18 months. Results: The vaccine Q beta-Der p 1 was well tolerated. Significant IgG responses were observed 4 weeks after a single injection. Individuals receiving 50 mu g of the vaccine had significantly higher IgG titers than those vaccinated with 10 mu g. However, the route of immunization (subcutaneous vs intramuscular) had no effect. In the 50-mu g dose group, strong antibody responses against Der p 1 with average titers of 1:2000 were obtained. Conclusion: Vaccination with a peptide antigen covalently coupled to highly repetitive virus-like particles represents an adjuvant-free means of rapidly inducing high antibody titers in human subjects. Clinical implications: Allergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.