Potent adaptive immune responses induced against HIV-1 gp140 and influenza virus HA by a polyanionic carbomer.
Carbopol is a polyanionic carbomer gel used in man for a variety of topical applications and drug delivery purposes. Here we show that subcutaneous administration of carbopol with glycoprotein antigens elicits unusually strong specific adaptive immune responses in mice. Recombinant soluble HIV-1 envelope glycoprotein (Env)-based antigen formulated in carbopol was at least as potent at stimulating Env-specific B and T cell responses as Freund's Complete Adjuvant, and significantly more potent than aluminium salts. The antigen-specific T cell immune response elicited both Th1 and Th2 cytokines including high titers of IFN-gamma, IL-2 and IL-4, and drove a Th1 isotype-switched antibody response. Mice immunized with a low dose of purified influenza HA in carbopol generated high titers of anti-HA antibodies and were protected from lethal challenge and disease with live virus. Similarly, immunization of mice with the melanoma cell line B16F10 formulated in carbopol significantly delayed tumor growth. We propose that carbopol, or related cross-linked polyacrylic acid analogues, may have promise for use as systemic vaccine adjuvants in man.
The Sir William Dunn School of Pathology, The University of Oxford, South Parks Road, Oxford, UK.
George
G
Krashias
Anna-Katharina
AK
Simon
Frank
F
Wegmann
Wai-Ling
WL
Kok
Ling-Pei
LP
Ho
David
D
Stevens
John
J
Skehel
Jonathan L
JL
Heeney
Amin E
AE
Moghaddam
Quentin J
QJ
Sattentau
D000180:Acrylic Resins; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D019496:Cancer Vaccines / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage*; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage* / Q000276:immunology*; D007279:Injections, Subcutaneous; D008297:Male; D008545:Melanoma / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D011145:Polyvinyls / Q000008:administration & dosage*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000276:immunology*
D000180:Acrylic Resins; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019496:Cancer Vaccines; D016207:Cytokines; D004337:Drug Carriers; D015483:HIV Antibodies; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011145:Polyvinyls; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C006912:carboxypolymethylene