Liposomal adjuvanticity: effect of encapsulation and surface-linkage on antibody production and proliferative response.
The immunoadjuvanticity of liposomal antigens, namely encapsulated and surface-linked conalbumin, was studied at different levels of an immune response including immunoglobulin production, blastogenic response and lymphokine production in sensitization conditions compatible with vaccine designs. The results demonstrated that both liposomal formulations stimulate all properties analyzed with respect to free antigen but significantly differ in some of their inductive capabilities, suggesting that they follow different routes in the immune network. Thus, although both liposomal antigens are capable of inducing potent humoral responses characterized by increased production of IgM and IgG2a, covalently linked antigen stimulates a quasi-polyclonal blastogenic response accompanied by the simultaneous secretion of IL-2 and IFN gamma, while encapsulated antigen which is less blastogenic mainly induces IL-2 secretion. We can conclude that: first, both antigenic formulations induce a Th1 type of activation and might therefore potentiate cell-mediated immunity, but surface-linkage favors a more rapid maturation of the response and a much more intense help induction. Second, although a strong adjuvanticity can be observed whatever the route of sensitization, namely intraperitoneally, intravenously or subcutaneously, the intravenous injections induce the better potentiation. The in vitro data were all compared to those obtained with naïve mice, allowing dissociation of the contribution of the in vitro rechallenge from that of the in vivo immunization. These differences observed between the liposomal antigens might be taken advantage of while formulating vaccines specifically suited to meet required needs and suggest that covalently linked antigen might be particularly useful in situations where induction of cell-mediated immunity is of prime importance.
Shahum
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Département de Chimie-Biologie, Université de Québec à Trois-Rivières, Trois-Rivières, Canada.
Thérien
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D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003207:Conalbumin / Q000008:administration & dosage / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000166:cytology
D000276:Adjuvants, Immunologic; D000941:Antigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007376:Interleukin-2; D008081:Liposomes; D003207:Conalbumin; D015847:Interleukin-4; D007371:Interferon-gamma