Activation of dendritic cells and induction of T cell responses by HPV 16 L1/E7 chimeric virus-like particles are enhanced by CpG ODN or sorbitol

• Published in: Antiviral therapy Vol. 9; no. 4; pp. 479 - 489
• Main Authors: FREYSCHMIDT, Eva-Jasmin, ALONSO, Angel, HARTMANN, Gunther, GISSMANN, Lutz
• Format: Journal Article
• Language: English
• Published: London International Medical Press 01.08.2004
• Subjects: Adjuvants, Immunologic - pharmacology; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; B7-1 Antigen - biosynthesis; Biological and medical sciences; Bone Marrow - drug effects; Bone Marrow - immunology; Bone Marrow - virology; Capsid Proteins - genetics; Capsid Proteins - immunology; CD40 Antigens - biosynthesis; Cells, Cultured; CpG Islands; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - virology; Dose-Response Relationship, Immunologic; Epitopes, T-Lymphocyte - biosynthesis; Female; Histocompatibility Antigens Class II - biosynthesis; Intercellular Adhesion Molecule-1 - biosynthesis; Lipopolysaccharides - pharmacology; Lymphocyte Activation - drug effects; Medical sciences; Mice; Mice, Inbred C57BL; Oligodeoxyribonucleotides - pharmacology; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - immunology; Oncogene Proteins, Viral - pharmacology; Papillomaviridae - pathogenicity; Papillomavirus E7 Proteins; Pharmacology. Drug treatments; Sorbitol - pharmacology; T-Lymphocytes, Cytotoxic - drug effects; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - virology; Sorbitol; Dendritic cell; Induction; Virus like particle; Activation; Laxative; Papovaviridae; Papillomavirus; Virus; Diuretic; Human papillomavirus 16; Human papillomavirus; T-Lymphocyte
• ISSN: 1359-6535; 2040-2058
• DOI: 10.1177/135965350400900419

Chimeric human papillomavirus-like particles, consisting of human papillomavirus (HPV) 16 L1-E7 fusion proteins [HPV 16 L1/E7 chimeric virus-like particles (CVLP)], are a vaccine candidate for treatment and prevention of cervical cancer. Although in preclinical studies CVLPs were shown to induce neutralizing antibodies and L1- and E7-specific T cell responses, the results of a recent clinical trial emphasized the need of improved immunogenicity of CVLPs. Here we studied the interaction of HPV 16 L1/E7 CVLPs with mouse bone marrow-derived dendritic cells (BMDCs) activated with different immune adjuvants. We found that lipopolysaccharides (LPS), unmethylated CpG motifs (CpG ODN) and sorbitol enhanced CVLP-induced stimulation of C57BL/6 mouse BMDCs as revealed by increased levels of CD40, CD80, MHC II and CD54 at the cell surface. CpG ODN and sorbitol also enhanced the presentation of Db-restricted cytotoxic T lymphocyte epitopes to HPV 16 L1- or E7-specific T lymphocytes after loading of CVLPs onto BMDCs. Treatment of BMDCs with CpG ODN in combination with CVLPs improved in vitro priming of naive T lymphocytes by CVLP-loaded BMDCs. In vivo, CVLP-loaded BMDCs were more immunogenic as compared with injection of CVLPs alone. CpG ODN and sorbitol further enhanced priming of antigen-specific T cell responses. Our data demonstrate that CpG ODN- or sorbitol-activated BMDCs substantially increase the immunogenicity of CVLPs. Implementing our results in clinical trial protocols may lead to improved activity of therapeutic HPV vaccines for the treatment of HPV-induced cancer.