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

BackgroundIn 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 Qβ (Qβ-Der p 1).ObjectiveWe evaluated the safety and immunogenicity of Qβ-Der p 1 in human subjects and compared different doses and routes of immunization.MethodsIn a phase I trial 24 healthy volunteers were randomly assigned to one of 4 treatment groups. Group 1 received 50 μg of Qβ-Der p 1 intramuscularly, group 2 received 50 μg of Qβ-Der p 1 subcutaneously, group 3 received 10 μg of Qβ-Der p 1 intramuscularly, and group 4 received 10 μg of Qβ-Der p 1 subcutaneously. Boosting immunizations with 10 μg were given after 1 and 3 months. Antibody titers were measured after 1, 3, 4, 6, 12, and 18 months.ResultsThe vaccine Qβ-Der p 1 was well tolerated. Significant IgG responses were observed 4 weeks after a single injection. Individuals receiving 50 μg of the vaccine had significantly higher IgG titers than those vaccinated with 10 μg. However, the route of immunization (subcutaneous vs intramuscular) had no effect. In the 50-μg dose group, strong antibody responses against Der p 1 with average titers of 1:2000 were obtained.ConclusionVaccination 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 implicationsAllergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.