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

• Published in: Journal of Allergy and Clinical Immunology Vol. 117; no. 6; pp. 1470 - 1476
• Main Authors: Kündig, Thomas M., Senti, Gabriela, Schnetzler, Gabriel, Wolf, Charles, Prinz Vavricka, Bettina M., Fulurija, Alma, Hennecke, Frank, Sladko, Katja, Jennings, Gary T., Bachmann, Martin F.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.06.2006; Elsevier; Elsevier Limited
• Subjects: Adolescent; Adult; Allolevivirus - immunology; Amino Acid Sequence; Animals; Antibodies, Viral - biosynthesis; Antigens, Dermatophagoides - administration & dosage; Antigens, Dermatophagoides - immunology; Arthropod Proteins; Biological and medical sciences; Blood & organ donations; clinical trial; Cysteine Endopeptidases; Der p 1; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Good Manufacturing Practice; Hepatitis; Hepatitis B Core Antigens - administration & dosage; Hepatitis B Core Antigens - adverse effects; Hepatitis B Core Antigens - immunology; Hepatitis B Vaccines - administration & dosage; Hepatitis B Vaccines - adverse effects; Hepatitis B Vaccines - immunology; Human subjects; Humans; Immunoglobulin G - biosynthesis; Immunopathology; immunotherapy; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Peptide Fragments - administration & dosage; Peptide Fragments - adverse effects; Peptide Fragments - immunology; Peptides; Proteins; Pyroglyphidae - immunology; Regulatory approval; Vaccines; Vaccines, Combined - administration & dosage; Vaccines, Combined - adverse effects; Vaccines, Combined - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - adverse effects; Viral Vaccines - immunology; Virion - immunology; virus-like particle; Viruses; clinical trial; Der p 1; virus-like particle; immunotherapy; GMP; VLP; Qβ-Der p 1; Human; Immunopathology; Peptides; Virus like particle; Acaridida; Dermatophagoides pteronyssinus; Acariformes; Arachnida; Immunology; Treatment; Acari; Arthropoda; Immunotherapy; Pyroglyphidae; Adult; Clinical trial; Invertebrata
• ISSN: 0091-6749; 1097-6825; 1365-2567
• DOI: 10.1016/j.jaci.2006.01.040

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 Qβ (Qβ-Der p 1). We evaluated the safety and immunogenicity of Qβ-Der p 1 in human subjects and compared different doses and routes of immunization. In 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. The 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. 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. Allergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.