Enhancement of IL-10 bioactivity using an IL-10 peptide-based vaccine exacerbates Leishmania major infection and improves airway inflammation in mice.
IL-10 is a regulatory cytokine that plays important roles in promoting disease progression in cutaneous leishmaniasis and suppressing allergic responses in asthma. We sought to develop an IL-10 peptide-based vaccine for the control of IL-10-related diseases. To break self-tolerance, hepatitis B core antigen (HBcAg) was used as a carrier. The vaccine was prepared by inserting a peptide derived from mouse IL-10 into the carrier using gene recombination methods. This vaccine presented as virus-like particles, bound to polyclonal anti-IL-10 antibodies, and induced high titers of IL-10-specific IgG. The in vivo effects of the vaccine were investigated in a murine model of cutaneous leishmaniasis. Unexpectedly, vaccinated mice developed larger cutaneous lesions, harbored significantly more parasites, and cells from lymph nodes produced higher amounts of parasite-specific IL-4, IL-10 and IFN-gamma in cultures. Further in vitro studies showed that serum IL-10-specific IgG from vaccinated mice significantly enhanced IL-10 bioactivity dose-dependently. This enhancing effect was confirmed in OVA-induced asthmatic mice. Vaccinated mice exhibited a significant decrease in airway eosinophils, lung inflammation, goblet hyperplasia, and levels of serum OVA-specific IgE, compared to control mice. We concluded that the IL-10 vaccine enhances the bioactivity of IL-10 in vitro and in vivo, providing a potential therapeutic approach in diseases associated with insufficient IL-10 production.
Zhou
Gang
G
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.
Ma
Yanbing
Y
Jia
Ping
P
Guan
Qingdong
Q
Uzonna
Jude E
JE
Peng
Zhikang
Z
D000818:Animals; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000276:immunology; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000188:drug therapy / Q000276:immunology; D011994:Recombinant Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D022223:Vaccines, Subunit / Q000276:immunology*
D001323:Autoantibodies; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma