Immunization with an HPV-16 L1-based chimeric virus-like particle containing HPV-16 E6 and E7 epitopes elicits long-lasting prophylactic and therapeutic efficacy in an HPV-16 tumor mice model

• Published in: Archives of virology 2014-02, Vol.159 (2), p.291-305
• Main Authors: Monroy-García, Alberto, Gómez-Lim, Miguel Angel, Weiss-Steider, Benny, Hernández-Montes, Jorge, Huerta-Yepez, Sara, Rangel-Santiago, Jesús F, Santiago-Osorio, Edelmiro, Mora García, María de Lourdes
• Format: Article
• Language: English
• Subjects: Amino acids; Animals; Antibodies; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigens; Biomedical and Life Sciences; Biomedicine; Capsid Proteins - genetics; Capsid Proteins - immunology; Carcinoma - immunology; Carcinoma - prevention & control; Carcinoma - therapy; Cervical cancer; Cytotoxicity; Disease Models, Animal; epitopes; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; Female; Human papillomavirus; immunization; immunoglobulin G; Infections; Infectious Diseases; Medical Microbiology; medicinal properties; Mice; Mice, Inbred C57BL; neutralizing antibodies; Oncogene Proteins, Viral - genetics; Oncogene Proteins, Viral - immunology; Original Article; Papillomavirus E7 Proteins - genetics; Papillomavirus E7 Proteins - immunology; Papillomavirus Infections - complications; Papillomavirus Infections - immunology; Papillomavirus Infections - prevention & control; Papillomavirus Vaccines - administration & dosage; Papillomavirus Vaccines - genetics; Papillomavirus Vaccines - immunology; Peptides; Proteins; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Repressor Proteins - genetics; Repressor Proteins - immunology; Transgenic plants; Tumors; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - genetics; Vaccines, Virus-Like Particle - immunology; Virology; virus-like particles
• ISSN: 0304-8608; 1432-8798
• DOI: 10.1007/s00705-013-1819-z

HPV L1-based virus-like particles vaccines (VLPs) efficiently induce temporary prophylactic activity through the induction of neutralizing antibodies; however, VLPs that can provide prophylactic as well as therapeutic properties for longer periods of time are needed. For this purpose, we generated a novel HPV 16 L1-based chimeric virus-like particle (cVLP) produced in plants that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus. In the present study, we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by immunization with these cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice. We observed that these cVLPs induced persistent IgG antibodies for over 12 months, with reactivity and neutralizing activity for VLPs composed of only the HPV-16 L1 protein. Efficient protection for long periods of time and inhibition of tumor growth induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins, as well as significant tumor reduction (57 %), were observed in mice immunized with these cVLPs. Finally, we discuss the possibility that chimeric particles of the type described in this work may be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.