Many cervical cancers express the E7 protein of human papillomavirus 16 as a tumor-specific Ag (TSA). To establish the role of E7-specific T cell help in CD8+ CTL-mediated tumor regression, C57BL/6J mice were immunized with E7 protein or with a peptide (GF001) comprising a minimal CTL epitope of E7, together with different adjuvants. Immunized mice were challenged with an E7-expressing tumor cell line, EL4.E7. Growth of EL4.E7 was reduced following immunization with E7 and Quil-A (an adjuvant that induced a Th1-type response to E7) or with GF001 and Quil-A. Depletion of CD8+ cells, but not CD4+ cells, from an immunized animal abrogated protection, confirming that E7-specific CTL are necessary and sufficient for TSA-specific protection in this model. Immunization with E7 and Algammulin (an alum-based adjuvant) induced a Th2-like response and provided no tumor protection. To investigate whether a Th2 T helper response to E7 could prevent the development of an E7-specific CTL-mediated protection, mice were simultaneously immunized with E7/Algammulin and GF001/Quil-A or, alternatively, were immunized with GF001/Quil-A 8 wk after immunization with E7/Algammulin. Tumor protection was observed in each case. We conclude that an established Th2 response to a TSA does not prevent the development of TSA-specific tumor protective CTL.

1998-05-01·Scandinavian Journal of Immunology4区 · 医学

Vaccine‐Induced Th1‐Type Responses are Dominant over Th2‐Type Responses in the Short Term whereas Pre‐existing Th2 Responses are Dominant in the Longer Term

4区 · 医学

Article

作者: Frazer ; Fernando ; Stewart ; Tindle

The effect of adjuvant on induction of human papillomavirus type 16 E7 protein‐specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG)2a antibody was studied in C57BL/6 J mice immunized with various adjuvants and E7 protein. Quil‐A adjuvant, but not complete Freund's adjuvant (CFA) or Algammulin, induced a T‐helper 1 (Th1)‐type response to E7, which was characterized by CTL activity against a tumour cell line transfected with E7 protein and by E7‐specific IgG2a. All tested adjuvants elicited comparable levels of E7‐specific IgG1. The longest duration and greatest magnitude of CTL response was seen following two immunizations with the highest dose of E7 and Quil‐A. Simultaneous immunization with a Th1 and a T helper 2 (Th2)‐promoting adjuvant gave a Th1‐type response. However, E7 and Quil‐A were unable to induce a Th1‐type response (as measured by the inability to generate anti‐E7 IgG2a antibody) in animals with a pre‐existing Th2‐type response to E7. These results suggest that saponin adjuvants may be suitable for immunotherapy in humans where a Th1‐type response is sought, provided that there is no pre‐existing Th2‐type response to the antigen.

1998-01-01·Developments in biological standardization

Influence of several adjuvants on the immune response against a recombinant meningococcal high molecular weight antigen.

Article

作者: Nazábal, C ; González, S ; Viña, L ; Caballero, E

Studying outer membrane proteins as vaccine candidates, our group has previously isolated, cloned, and expressed in Escherichia coli the gene encoding for a high molecular weight protein (P64k), common to many meningococcal strains. To continue the characterisation of this meningococcal antigen, we have evaluated its immunogenicity in mice alone or combined with several commercially-available adjuvants. We used as an adjuvant aluminium hydroxide (Alhydrogel and Rehydragel), aluminium phosphate, Algammulin, crude saponin, the saponin Quil A, dimethyl-dioctadecyl ammonium bromide (DDA), Freund's adjuvant, and Montanide 888. The antibody titres against the recombinant protein and whole meningococci elicited with these adjuvants were compared. We found that Quil A produced the highest titres against the recombinant P64k. Algammulin and the quaternary ammonium compound DDA induced the highest levels of antibodies against meningococci. We analysed the recognition of a set of linear peptides by antisera prepared against the protein combined with some of the adjuvants. The responses depended on the adjuvant used and the results have been confirmed by epitope mapping using overlapping peptides synthesised on pins.

100 项与 Algammulin(Australian National University Library) 相关的药物交易

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