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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

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Abstract

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.

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Acknowledgments

We thankfully acknowledge the excellent technical assistance of Ernesto Javier Rivera Rosales. We are indebted to CONACYT for support to AMG (grant 84071), MAGL (grant 83732) and MLMG (grant 82827); and Fondo de Investigación en Salud-IMSS for support to AMG. Protocolos 60 and 617 and 876 are gratefully acknowledged.

Conflict of interest

The authors declare that they do not have any conflict of interest.

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Authors and Affiliations

  1. Unidad de Investigación Médica en Enfermedades Oncológicas, IMSS, CMN SXXI, Mexico, D.F., Mexico

    Alberto Monroy-García

  2. Laboratorio de Inmunobiología, Lab, 3 PB, Unidad de Investigación en Diferenciación Celular y Cáncer, Facultad de Estudios Superiores Zaragoza, UMIEZ, Campus II, UNAM, Batalla 5 de mayo s/n, Col. E. Oriente, Esquina Fuerte Loreto, Iztapalapa, CP 09230, Mexico, D.F., Mexico

    Alberto Monroy-García, Benny Weiss-Steider, Jorge Hernández-Montes & María de Lourdes Mora García

  3. Unidad Irapuato, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Guanajuato, Mexico

    Miguel Angel Gómez-Lim

  4. Unidad de Investigación en Enfermedades Oncológicas, Hospital Infantil de México, Federico Gómez, Mexico City, Mexico

    Sara Huerta-Yepez & Jesús F. Rangel-Santiago

  5. Laboratorio de Hematopoiesis y Leucemia, Unidad de Investigación en Diferenciación Celular y Cáncer, FES-Zaragoza, UMIEZ, UNAM, Mexico, D.F., Mexico

    Edelmiro Santiago-Osorio

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  1. Alberto Monroy-García
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Monroy-García, A., Gómez-Lim, M.A., Weiss-Steider, B. et al. 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. Arch Virol 159, 291–305 (2014). https://doi.org/10.1007/s00705-013-1819-z

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