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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 Qbeta (Qbeta-Der p 1). OBJECTIVE: We evaluated the safety and immunogenicity of Qbeta-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 1 received 50 microg of Qbeta-Der p 1 intramuscularly, group 2 received 50 microg of Qbeta-Der p 1 subcutaneously, group 3 received 10 microg of Qbeta-Der p 1 intramuscularly, and group 4 received 10 microg of Qbeta-Der p 1 subcutaneously. Boosting immunizations with 10 microg were given after 1 and 3 months. Antibody titers were measured after 1, 3, 4, 6, 12, and 18 months. RESULTS: The vaccine Qbeta-Der p 1 was well tolerated. Significant IgG responses were observed 4 weeks after a single injection. Individuals receiving 50 microg of the vaccine had significantly higher IgG titers than those vaccinated with 10 microg. However, the route of immunization (subcutaneous vs intramuscular) had no effect. In the 50-microg 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.

Original publication

DOI

10.1016/j.jaci.2006.01.040

Type

Journal article

Journal

J Allergy Clin Immunol

Publication Date

06/2006

Volume

117

Pages

1470 - 1476

Keywords

Adolescent, Adult, Allolevivirus, Amino Acid Sequence, Animals, Antibodies, Viral, Antigens, Dermatophagoides, Arthropod Proteins, Cysteine Endopeptidases, Female, Hepatitis B Core Antigens, Hepatitis B Vaccines, Humans, Immunoglobulin G, Male, Middle Aged, Molecular Sequence Data, Peptide Fragments, Pyroglyphidae, Vaccines, Combined, Viral Vaccines, Virion