Novel recombinant interleukin-13 peptide-based vaccine reduces airway allergic inflammatory responses in mice.
BACKGROUND
Interleukin (IL)-13 plays a pivotal role in the pathogenesis of allergic asthma. Passive administration of its monoclonal antibody or soluble receptor to block overproduced IL-13 has been proven to be effective in controlling airway allergic responses in animal models, but these approaches have disadvantages of short half-lives, high costs, and possible adverse effects.


OBJECTIVE
We sought to develop a novel therapeutic strategy through constructing an IL-13 peptide-based vaccine for blocking IL-13 on a persistent effect basis and to evaluate its in vivo effects using a murine model.


METHODS
To break self-tolerance, truncated hepatitis B core antigen was used as a carrier. Vaccine was prepared by inserting a peptide derived from the receptor binding site of mouse IL-13 into the immunodominant epitope region of the carrier using gene recombination methods. Mice received vaccine subcutaneously three times, and then subjected to intraperitoneal sensitization and intranasal challenge with ovalbumin. Control animals received carrier or saline in place of vaccine.


RESULTS
The vaccine presented as virus-like particles and induced sustained and high titered IL-13-specific IgG without the use of conventional adjuvant. Vaccination significantly suppressed ovalbumin-induced inflammatory cell number, and IL-13 and IL-5 levels in bronchoalveolar lavage fluids. Serum total and ovalbumin-specific IgE were also significantly inhibited. Moreover, allergen-induced goblet cell hyperplasia, lung tissue inflammatory cell infiltration, and pulmonary hyperresponsiveness to inhaled methacholine were significantly suppressed in vaccinated mice.


CONCLUSIONS
Our data indicate that IL-13 peptide-based vaccines could be an effective therapeutic approach in the treatment of asthma.
Ma
Yanbing
Y
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
HayGlass
Kent T
KT
Becker
Allan B
AB
Fan
Yijun
Y
Yang
Xi
X
Basu
Sujata
S
Srinivasan
Ganesh
G
Simons
F Estelle R
FE
Halayko
Andrew J
AJ
Peng
Zhikang
Z
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001249:Asthma / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005260:Female; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007167:Immunotherapy / Q000379:methods*; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D012130:Respiratory Hypersensitivity / Q000628:therapy*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D018793:Interleukin-13; D019409:Interleukin-15; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D007073:Immunoglobulin E