title: TLR7 imidazoquinoline ligand 3M-019 is a potent adjuvant for pure protein prototype vaccines.
abstract: Cancer vaccines, while theoretically attractive, present difficult challenges that must be overcome to be effective. Cancer vaccines are often poorly immunogenic and may require augmentation of immunogenicity through the use of adjuvants and/or immune response modifiers. Toll-like receptor (TLR) ligands are a relatively new class of immune response modifiers that may have great potential in inducing and augmenting both cellular and humoral immunity to vaccines. TLR7 ligands produce strong cellular responses and specific IgG2a and IgG2b antibody responses to protein immunogens. This study shows that a new TLR7 ligand, 3M-019, in combination with liposomes produces very strong immune responses to a pure protein prototype vaccine in mice. Female C57BL/6 mice were immunized subcutaneously with ovalbumin (OVA, 0.1 mg/dose) weekly 4x. Some groups were immunized to OVA plus 3M-019 or to OVA plus 3M-019 encapsulated in liposomes. Both antibody and cellular immune responses against OVA were measured after either two or four immunizations. Anti-OVA IgG antibody responses were significantly increased after two immunizations and were substantially higher after four immunizations in mice immunized with OVA combined with 3M-019. Encapsulation in liposomes further augmented antibody responses. IgM responses, on the other hand, were lowered by 3M-019. OVA-specific IgG2a levels were increased 625-fold by 3M-019 in liposomes compared to OVA alone, while anti-OVA IgG2b levels were over 3,000 times higher. In both cases encapsulation of 3M-019 in liposomes was stronger than either liposomes alone or 3M-019 without liposomes. Cellular immune responses were likewise increased by 3M-019 but further enhanced when it was encapsulated in liposomes. The lack of toxicity also indicates that this combination may by safe, effective method to boost immune response to cancer vaccines.
authors.affiliation: Hunter College School of Health Sciences, New York, NY, USA. djohnsto@hunter.cuny.edu
authors.forename: Dean
authors.initials: D
authors.lastname: Johnston
authors.forename: Bushra
authors.initials: B
authors.lastname: Zaidi
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Bystryn
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004339:Drug Compounding; D004353:Drug Evaluation, Preclinical; D005260:Female; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011804:Quinolines / Q000008:administration & dosage / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000187:drug effects* / Q000502:physiology
chemical_list: C521518:3M-019; C095471:4-amino-alpha,alpha,2-trimethyl-1H-imidazo(4,5-c)quinoline-1-ethanol; D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D007093:Imidazoles; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008081:Liposomes; D008562:Membrane Glycoproteins; D011804:Quinolines; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D007371:Interferon-gamma; D010047:Ovalbumin