Adjuvants for a New Generation of Vaccines

Abstract

for a new generation of vaccines. Can J Infect Dis 1992;3(Suppl B):84B-93B. Subunit antigens of viruses and other infectious agents in their natural configuration can be produced by recombinant DNA technology. To elicit protective immunity such antigens have to be admirustered with adjuvants that elicit cell-mediated immunity, including genetically restricted cytotoxicity, and that pr oduce high alfmity antibodies of protective isotypes. Antibodies of such isotypes (immunoglobulin G2a [IgG2a] in the mouse and IgG I in humans) efficiently activate complement and eiTect antibody-dependent cell-mediated cytotoxicity. Naturally occurring adjuvants such as lipopolysaccharide and muramyl dipeptide (MOP) are pyrogenic and produce uveitis and arthritis in susceptible experimental animal and human recipients. Synthetic analogues of MOP and monophosphoryl lipid A (MPL) retain adjuvant activity with reduced side eiTects. Adjuvants increase the expression of class II major histocompatibility complex on antigen-presenting cells and cytokine production: interferon-gamma augments the production of IgG2a antibod ies in the mouse. Dispersion of antigens in water-oil emulsions, immunestimulating complexes or liposomes also increases immunogenicity. at least partly by targeting antigens to antigen-presenting cells. Inclusion of MOP analogues or MPL in such systems constitutes adjuvant formu lations. such as MOP-A. When used with a variety of recombinant and other subunit antigens. such adjuvants elicit protective immunity in experimental animals. This strategy improves vaccines already in use (eg, inJl uenza and hepatitis B) and makes possible new vaccines (herpesviruses, simian and human immunodeficiency viruses. respiratory syncytial virus and acellular pertussis).

Novel Strategies in the Design and Production of Vaccines

“…Stimulation ofTh 1 type response leads to a cell-mediated immune response (delayed type hypersensitivity) and production of relatively high levels of IgG2a antibodies in mice. In recent years several adjuvant formulations including Freund's complete adjuvant, Syntex adjuvant formulation-I, muramyl dipeptide, lipopolysaccharide, monophosphoryl lipid A, Y inulin, stearyl tyrosine, liposomes, QS21 have been shown to stimulate the Th1 type response in mice (Allison and Byars, 1990;Audibert and Lise, 1993;Kensil et aI., 1993;Cooper, 1994;. Antigen delivered by Salmonella typhimurium for mucosal immunization also elicited Thl type response in mice (Staats et aI., 1994).…”

Proteína de 18kDa de Mycobacterium leprae: um modelo de carregadora para vacinas de segunda geração

“…Inicialmente descritos como veículos para substâncias biologicamente ativas (New, 1990), foram propostos há 25 anos como imunoadjuvantes (Allison & Gregoriadis, 1974), em função de suas características como carregadores e apresentadores de antígenos. Sua composição lipídica, o método de preparo e de associação de antígeno variam muito (New, 1990;Allison & Byars, 1990), permitindo a obtenção de formulações diferentes para os mais diversos fins.…”