RESUMO
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.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/administração & dosagem , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Polivinil/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/administração & dosagem , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Resinas Acrílicas , Animais , Anticorpos Antivirais/sangue , Vacinas Anticâncer/imunologia , Células Cultivadas , Citocinas/metabolismo , Feminino , Anticorpos Anti-HIV/sangue , Injeções Subcutâneas , Masculino , Melanoma/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/prevenção & controle , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Fred Brown was a major figure in British and international virology during most of the latter half of the twentieth century. He brought to the subject a rigorous and critical attitude acquired during his early training in chemistry. In addition, he was passionately interested in the practical application of his work and that of others to the prevention and alleviation of disease. He always believed that his research would make a significant contribution to the welfare of agricultural livestock. He is best known for his pioneering work on foot-and-mouth disease virus, the causative agent for the most important disease of domestic livestock globally. However, he also made seminal contributions to the study of many other viruses of veterinary importance.