Topical imiquimod is a potent adjuvant to a weakly-immunogenic protein prototype vaccine.
A major challenge in the development of more effective vaccines for cancer and other diseases is the development of potent adjuvants that can strongly, simply and safely enhance vaccine immunogenicity. Adjuvants that preferentially enhance Th1 type of responses are particularly desirable, as these responses are believed to play the major role in immune resistance to cancer. This study describes the ability of topical application of imiquimod to act as a potent, safe and simple vaccine adjuvant in mice. Groups of C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1mg/dose) weekly x 4. Imiquimod in a 5% cream formulation was rubbed into the skin over the injection site for 15s to give a dose of approximately 1mg/treatment following each immunization. Control mice were immunized with OVA alone, with irradiated E.G7-OVA cells (that express ovalbumin), with OVA encapsulated in liposomes, or to PBS. Topical imiquimod enhanced anti-OVA antibody responses 100-fold and markedly increased cellular responses compared to mice not given imiquimod. The responses were shifted towards a Th1 phenotype, with marked enhancement of IgG2a, IgG2b, and CD8+ T cell responses and concomitant suppression of IgM and IgG1 responses. More frequent topical applications of imiquimod further enhanced both antibody and cellular responses. There was no detectable local or systemic toxicity associated with treatment. These results indicate that topical imiquimod can safely and strongly enhance both antibody and CD8+ T cell response to OVA immunization, and suggest that it may provide a simple, safe and effective way to enhance the immunogenicity of vaccines in general.
Johnston
Dean
D
Hunter College School of Health Sciences, 425 East 25th Street, New York NY 10010, USA. djohnsto@hunter.cuny.edu
Bystryn
Jean-Claude
JC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity; D000287:Administration, Topical; D000634:Aminoquinolines / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000077271:Imiquimod; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007279:Injections, Subcutaneous; D007372:Interferons / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination / Q000379:methods*; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D000906:Antibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D014612:Vaccines; D010047:Ovalbumin; D007372:Interferons; D000077271:Imiquimod