A vaccine conjugate of 'ISCAR' immunocarrier and peptide epitopes of the E7 cervical cancer-associated protein of human papillomavirus type 16 elicits specific Th1- and Th2-type responses in immunized mice in the absence of oil-based adjuvants

Clin Exp Immunol. 1995 Aug;101(2):265-71. doi: 10.1111/j.1365-2249.1995.tb08349.x.

Abstract

TraT protein, known as ISCAR (= Immunostimulatory Carrier), is one of a family of integral membrane proteins (Imps) of Escherichia coli representing powerful carrier molecules which when injected into experimental animals generate substantial antibody and T proliferative responses to molecules conjugated to it. We extend these findings to show that ISCAR functions to stimulate Th1- and Th2-type responses, including specific cytotoxic T cells and tumour protection. We report here that by conjugating to ISCAR a 19mer peptide containing linear B epitopes, a T helper (Th) epitope, and a H-2b-restricted T cytotoxic (CTL) epitope of E7 protein of human papillomavirus type 16 (HPV16), and immunizing C57B1/6 (H-2b) mice, we elicited (i) specific IgG2a and IgG1 antibodies; (ii) IL-2 and IL-4 production by specifically recalled lymph node cells in vitro; (iii) cytotoxic T lymphocytes which specifically killed both E7 peptide-pulsed, and whole E7 gene-transfected tumour target cells; and (iv) in vivo protection against an E7 gene-transfected tumour cell inoculum. These findings have implications for the design of vaccines to stimulate immune responses to endogenously processed target antigens (e.g. tumour-associated antigens) without the unwanted side effects of oil-based adjuvants. In addition they support the case for a E7-targeted therapeutic vaccine for HPV-associated human cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / blood
  • Antigens, Neoplasm / immunology
  • Bacterial Outer Membrane Proteins / immunology*
  • Epitopes / immunology*
  • Escherichia coli Proteins*
  • Female
  • Immunization
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Neoplasms, Experimental / prevention & control
  • Oncogene Proteins, Viral / immunology*
  • Papillomaviridae
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Vaccines, Conjugate / pharmacology
  • Viral Vaccines / pharmacology*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Antigens, Neoplasm
  • Bacterial Outer Membrane Proteins
  • Epitopes
  • Escherichia coli Proteins
  • Interleukin-2
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Papillomavirus Vaccines
  • TraT protein, E coli
  • Vaccines, Conjugate
  • Viral Vaccines
  • oncogene protein E7, Human papillomavirus type 16
  • Interleukin-4