Resiquimod and other immune response modifiers as vaccine adjuvants.
Synthetic immune response modifiers, such as resiquimod, are Toll-like receptor 7 and 8 agonists that act as vaccine adjuvants, enhancing antigen-specific antibody production and skewing immunity towards a Th1 response. These compounds stimulate dendritic cells to secrete cytokines, upregulate costimulatory molecule expression and enhance antigen presentation to T cells. The compounds have demonstrated vaccine adjuvant properties in a number of animal models. The adjuvant effects can be enhanced by measures that allow the drug to stay localized with the vaccine without quickly entering the systemic circulation. Clinical studies demonstrate that topical application of resiquimod and analogs is safe and effective at activating the local immune response. For injection, resiquimod or a similar compound may need to be formulated to allow for local immune activation without induction of systemic cytokines.
Tomai
Mark A
MA
3M Drug Delivery Systems, 3M Center, 275-3E-10 St Paul, MN 55144, USA. matomai@mmm.com
Miller
Richard L
RL
Lipson
Kenneth E
KE
Kieper
William C
WC
Zarraga
Isidro E
IE
Vasilakos
John P
JP
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage* / Q000276:immunology; D007155:Immunologic Factors / Q000008:administration & dosage* / Q000276:immunology; D014612:Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D007093:Imidazoles; D007155:Immunologic Factors; D014612:Vaccines; C402365:resiquimod