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

Scand J Immunol. 1998 May;47(5):459-65. doi: 10.1046/j.1365-3083.1998.00327.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antibody Formation / drug effects
  • Antibody Formation / immunology
  • Dose-Response Relationship, Immunologic
  • Female
  • Immunity, Cellular / drug effects
  • Immunity, Cellular / immunology
  • Immunotherapy
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Proteins, Viral / administration & dosage
  • Oncogene Proteins, Viral / immunology
  • Papillomavirus E7 Proteins
  • Papillomavirus Infections / therapy
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Time Factors
  • Tumor Virus Infections / therapy
  • Vaccination

Substances

  • Adjuvants, Immunologic
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • oncogene protein E7, Human papillomavirus type 16