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 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.


CONCLUSIONS
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.


CONCLUSIONS
Allergens coupled to virus-like particles can be used to enhance the efficiency of allergen-specific immunotherapy.
Kündig
Thomas M
TM
University of Zürich, Department of Dermatology, University Hospital Zürich, Switzerland. thomas.kuendig@usz.ch
Senti
Gabriela
G
Schnetzler
Gabriel
G
Wolf
Charles
C
Prinz Vavricka
Bettina M
BM
Fulurija
Alma
A
Hennecke
Frank
F
Sladko
Katja
K
Jennings
Gary T
GT
Bachmann
Martin F
MF
D000293:Adolescent; D000328:Adult; D017908:Allolevivirus / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology*; D060829:Arthropod Proteins; D003546:Cysteine Endopeptidases; D005260:Female; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D039981:Pyroglyphidae / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014771:Virion / Q000276:immunology*
D000914:Antibodies, Viral; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D010446:Peptide Fragments; D017778:Vaccines, Combined; D014765:Viral Vaccines; D003546:Cysteine Endopeptidases; C451162:Dermatophagoides pteronyssinus antigen p 1