Prime–boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X

TitlePrime–boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2016
AuthorsIlliano, E., Bissa M., Paolini F., Zanotto C., C. Morghen De Giuli, Franconi Rosella, Radaelli A., and Venuti A.
JournalVirus Research
Volume225
Pagination82-90
ISSN01681702
KeywordsAmino Acid Sequence, animal, animal cell, animal experiment, animal model, Animals, antibody response, article, cancer vaccine, Cancer Vaccines, capsid protein, Capsid Proteins, carcinogenicity, Cell Line, cellular distribution, coat protein, controlled study, cytoplasm, disease model, Disease Models, DNA, DNA immunization, DNA vaccine, drug efficacy, drug screening, E6 coat protein fusion protein, E6 protein, E7 coat protein fusion protein, Embryo, enzyme linked immunosorbent assay, Female, Fowlpox virus, Gene expression, gene vector, Genetic Vectors, genetics, homologous recombination, human, human cell, Human papillomavirus type 16, Humans, humoral immunity, hybrid protein, immunization, Immunofluorescence, immunogenicity, immunology, Mice, mouse, mutation, nonhuman, oncogene protein E7, Oncogene Proteins, oncoprotein, Papillomavirus E7 Proteins, Papillomavirus Vaccines, Potato virus S, Potato virus X, priority journal, protein E7, protein expression, protein transport, Recombinant Fusion Proteins, repressor protein, Repressor Proteins, Secondary, secondary immunization, tumor antigen, tumor cell inoculation, tumor growth, tumor volume, unclassified drug, Vaccines, Viral, virus fusion protein, virus recombinant, Wart virus vaccine, Western blotting, Xenograft Model Antitumor Assays
Abstract

The therapeutic antitumor potency of a prime–boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy. After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime–boost vaccine regimens. The humoral immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone. © 2016

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URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-84988810006&doi=10.1016%2fj.virusres.2016.09.011&partnerID=40&md5=434f6da87b22dbc19c5ec4bb8e946d45
DOI10.1016/j.virusres.2016.09.011