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.
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.
Fernando
G J
GJ
Centre for Immunology & Cancer Research, University of Queensland, Department of Medicine, Princess Alexandra Hospital, Brisbane, Australia.
Stewart
T J
TJ
Tindle
R W
RW
Frazer
I H
IH
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D007167:Immunotherapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000276:immunology; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000628:therapy; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014412:Tumor Virus Infections / Q000628:therapy; D014611:Vaccination
D000276:Adjuvants, Immunologic; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16