Phase 1 study of HPV16-specific immunotherapy with E6E7 fusion protein and ISCOMATRIX (TM) adjuvant in women with cervical intraepithelial neoplasia

Purpose: Persistent infection of cervical epithelium with high risk human papillomavirus (HPV) results in cervical intraepithelial neoplasia (CIN) from which squamous cancer of the cervix can arise. A study was undertaken to evaluate the safety and immunogenicity of an HPV 16 immunotherapeutic consisting of a mixture of HPV16 E6E7 fusion protein and ISCOMATRIX(TM) adjuvant (HPV16 Immunotherapeutic) for patients with CIN. Experimental design: Patients with CIN (n = 3 1) were recruited to a randomised blinded placebo controlled dose ranging study of immunotherapy. Results: Immunotherapy was well tolerated. Immunised subjects developed HPV16 E6E7 specific immunity. Antibody, delayed type hypersensitivity, in vitro cytokine release, and CD8 T cell responses to E6 and E7 proteins were each significantly greater in the immunised subjects than in placebo recipients. Loss of HPV16 DNA from the cervix was observed in some vaccine and placebo recipients. Conclusions : The HPV16 Immunotherapeutic comprising HPV16E6E7 fusion protein and ISCOMATRIX(TM) adjuvant is safe and induces vaccine antigen specific cell mediated immunity. (C) 2004 Elsevier Ltd. All rights reserved.

Early pregnancy factor in marsupials

Maternal recognition of pregnancy in marsupials occurs in more subtle ways than it does in eutherians. For instance, unlike in eutherians, the plasma progesterone profiles of pregnant and non-pregnant animals are similar during the luteal phase. It is typically during the brief luteal phase that both gestation and parturition occur in marsupials. Yet histological and physiological changes have been documented between gravid and non-gravid uteri in certain monovular marsupials and between pregnant and non-pregnant animals in polyovular marsupials. Early pregnancy factor (EPF), a 10.8-kDa serum protein known to be homologous to chaperonin 10, is associated with maternal immunosuppression, embryonic development and pregnancy in eutherian mammals. It has been reported in two Australian marsupials: the dasyurid Sminthopsis macroura and the phalangerid Trichosurus vulpecula. This paper documents its occurrence in the New World didelphid Monodelphis domestica. EPF is detectable by rosette inhibition assay in the peripheral circulation of pregnant but not of non-pregnant or pseudopregnant animals. Our work focuses on the embryo–maternal signalling role of EPF during pregnancy. Because progesterone-driven changes are similar in pregnant and non-pregnant marsupials, these animals are an excellent laboratory model in which to investigate the role of EPF in orchestrating the physiological changes necessary to sustain pregnancy.