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  • Title: Evaluation of HBs, HBc, and frCP virus-like particles for expression of human papillomavirus 16 E7 oncoprotein epitopes.
    Author: Pumpens P, Razanskas R, Pushko P, Renhof R, Gusars I, Skrastina D, Ose V, Borisova G, Sominskaya I, Petrovskis I, Jansons J, Sasnauskas K.
    Journal: Intervirology; 2002; 45(1):24-32. PubMed ID: 11937768.
    Abstract:
    OBJECTIVES: In an attempt to develop virus-like particles (VLPs) as experimental vaccine against human papilloma virus (HPV)-induced tumours, the HPV16 E7 oncoprotein epitopes spanning amino acid (aa) residues 35-98 were expressed on three proteins capable of VLP formation: hepatitis B virus (HBV) surface (HBs) and core (HBc) antigens, and RNA phage fr coats (frCP). METHODS: The profile of immunoglobulin isotypes induced in Balb/C mice after immunization with purified chimeric proteins was studied. RESULTS: The HBs*-E7(35-54) protein expressing E7 residues 35-54 between residues 139 and 142 of the HBs carrier formed HBs-like particles in Saccharomyces cerevisiae. The HBc Delta-E7(35-98), but not the frCP-E7(35-98), ensured VLP formation in Escherichia coli. In Balb/C mice, the HBs*-E7(35-54) VLPs predominantly induced an anti-E7 antibody, but not anti-HBs carrier response, whereas the HBc Delta-E7(35-98) VLPs induced a lower anti-E7 compared to anti-HBc carrier response. The frCP-E7(35-98) protein elicited equally high antibody responses to both E7 and frCP carrier. Analysis of the immunoglobulin G isotype profile of the antibodies induced by the E7-carrying chimeras showed that the HBs and frCP derivatives were capable of eliciting the Th1 and Th2 subsets of T helper cells, whereas the HBc-derived chimeras elicited only the Th2 subset. CONCLUSIONS: The HBs and HBc, but not frCP carriers support an efficient outcome for VLPs carrying the HPV16 E7 epitopes. All chimeric proteins may be regarded as potential vaccine candidates.
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