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

SUMMARY 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‐2 b ‐restricted T cytotoxic (CTL) epitope of E7 protein of human papillomavirus type 16 (HPV16), and immunizing C57B1/6 (H‐2 b ) 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.