Effect of IL-4 and IL-12 liposomal formulations on the induction of immune response to bovine herpesvirus type-1 glycoprotein D.
Activation of different T-helper (Th) responses following immunisation has profound and specific influences on the development of the immune response and on the ability of a vaccine to confer protection. Since cytokines are capable of influencing the stimulation of distinct T-cell responses, their encapsulation in vaccines should modulate antigen-specific immune responses. Unfortunately, the use of cytokines in vivo is hampered by their rapid clearance and inactivation. One possible solution to this problem is the use of liposomes to entrap both cytokines and antigen. This approach will not only protect the cytokine but will also deliver the two components simultaneously to the same site. The authors examined, therefore, the immune responses elicited by systemic immunisation of mice with liposome formulations containing a truncated form of bovine herpesvirus type-1 glycoprotein D (tgD) together with IL-4 or IL-12. Subcutaneous immunisation with liposomes containing tgD and IL-12 significantly enhanced the induction of antigen-specific cellular and humoral immune responses. These responses were characterised by an increase in IFN-gamma secreting cells and the induction of tgD-specific IgG2a antibodies. In contrast, encapsulation of IL-4 into tgD-liposomes did not enhance the humoral immune response to gD but significantly influenced the development of antigen-specific IL-4 secreting cells. Our results indicated that encapsulation of IL-12 into the liposomes was necessary for the systemic adjuvant effect and demonstrated the feasibility of using liposome technology and cytokines to manipulate the development of different antigen-specific Th subsets in vivo.
Baca-Estrada
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ME
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Canada.
Foldvari
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Snider
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van Drunen Littel-van den Hurk
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Babiuk
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LA
D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D002417:Cattle; D004339:Drug Compounding; D000939:Epitopes; D005260:Female; D022283:Herpesvirus Vaccines; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000276:immunology; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D008081:Liposomes; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
D000939:Epitopes; D022283:Herpesvirus Vaccines; D008081:Liposomes; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C039447:glycoprotein D, Human herpesvirus 1; C069093:herpes simplex virus-1 glycoprotein D vaccine; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma