title: Poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) is a potent enhancer of mixed Th1/Th2 immune responses in mice immunized with influenza virus antigens.
abstract: We investigated the ability of a novel polyphosphazene polyelectrolyte, poly[di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP) to enhance antigen-specific immune responses. BALB/c mice were immunized once subcutaneously with either bovine serum albumin (BSA) or influenza virus X:31 antigen alone, or in combination with PCEP, or either of the adjuvants poly[di(sodium carboxylatophenoxy)phosphazene] (PCPP) and alum. Both PCEP and PCPP significantly enhanced serum antigen-specific total IgG, IgG1 and IgG2a antibody titers, and these responses were highest in PCEP-immunized mice. Alum induced only a modest enhancement of antibody responses. Reducing the dose of X:31 antigen by 25-fold had no effect on antibody responses in mice immunized with PCPP and PCEP, but resulted in reduced titers in those immunized with alum. Analysis of X:31 antigen-specific cytokines revealed that alum and PCPP were associated with a predominantly IL-4 response. In contrast, PCEP was associated with production of both IFNgamma and IL-4. We conclude that PCEP is a potent enhancer of antigen-specific Th1 and Th2 immune responses and is a promising adjuvant for vaccine applications.
authors.affiliation: Vaccine & Infectious Disease Organization, 120 Veterinary Road, Saskatoon, SK, Canada S7N 5E3. george.mutwiri@usask.ca
authors.forename: George
authors.initials: G
authors.lastname: Mutwiri
authors.forename: Ponn
authors.initials: P
authors.lastname: Benjamin
authors.forename: Henry
authors.initials: H
authors.lastname: Soita
authors.forename: Hugh
authors.initials: H
authors.lastname: Townsend
authors.forename: Richard
authors.initials: R
authors.lastname: Yost
authors.forename: Bryan
authors.initials: B
authors.lastname: Roberts
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Andrianov
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Babiuk
mesh_terms: D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology* / Q000302:isolation & purification; D016207:Cytokines / Q000096:biosynthesis; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D007111:Immunity, Cellular / Q000187:drug effects*; D007074:Immunoglobulin G / Q000032:analysis / Q000096:biosynthesis; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010666:Phenylpropionates / Q000138:chemical synthesis / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D010666:Phenylpropionates; D011108:Polymers; C508285:poly(bis(carboxylatoethylphenoxy)phosphazene); C045869:polybis(carbophenoxypropane); D012710:Serum Albumin, Bovine; C041524:aluminum sulfate