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

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...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2004-02, Vol.319 (2), p.237-248
Main Authors: Herd, Karen A., Harvey, Tracey, Khromykh, Alexander A., Tindle, Robert W.
Format: Article
Language:English
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
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2003.10.032