Recombinant Kunjin virus replicon vaccines induce protective T-cell immunity against human papillomavirus 16 E7-expressing tumour

• Published in: Virology (New York, N.Y.) Vol. 319; no. 2; pp. 237 - 248
• Main Authors: Herd, Karen A., Harvey, Tracey, Khromykh, Alexander A., Tindle, Robert W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20-02-2004
• Subjects: Amino Acid Sequence; Animals; CTL; E7 oncoprotein; Epitopes - chemistry; Epitopes - immunology; Female; Flavivirus; Genetic Vectors - immunology; Human papillomavirus; Human papillomavirus 16; Immunity, Cellular; Immunization; Injections, Intramuscular; Kunjin virus; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Neoplasms, Experimental - prevention & control; Oncogene Proteins, Viral - immunology; Papillomaviridae - metabolism; Papillomavirus E7 Proteins; Papillomavirus Vaccines; Polyepitope; Replicon; Replicon - immunology; T-Lymphocytes, Cytotoxic - immunology; Tumour; Vaccines, Synthetic - administration & dosage; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; Virus-like particle vaccines; West Nile virus - immunology; Kunjin virus; Human papillomavirus; E7 oncoprotein; Virus-like particle vaccines; CTL; Tumour; Polyepitope; Replicon
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2003.10.032

The persistence of the E7 oncoprotein in transformed cells in human papillomavirus (HPV)-associated cervical cancer provides a tumour-specific antigen to which immunotherapeutic strategies may be directed. Self-replicating RNA (replicon) vaccine vectors derived from the flavivirus Kunjin (KUN) have recently been reported to induce T-cell immunity. Here, we report that inclusion of a CTL epitope of HPV16 E7 protein into a polyepitope encoded by a KUN vector induced E7-directed T-cell responses and protected mice against challenge with an E7-expressing epithelial tumour. We found replicon RNA packaged into virus-like particles to be more effective than naked replicon RNA or plasmid DNA constructed to allow replicon RNA transcription in vivo. Protective immunity was induced although the E7 CTL epitope was subdominant in the context of other CTL epitopes in the polyepitope. The results demonstrate the efficacy of the KUN replicon vector system for inducing protective immunity directed towards a virally encoded human tumour-specific antigen, and for inducing multi-epitopic CTL responses.