A novel HPV-16 L1 based chimeric virus-like particle containing HPV 16 E6 and E7 epitopes elicits a persistent specific antibody immune response and tumor regression.
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1
INSTITUTO MEXICANO DEL SEGURO SOCIAL, UIMEO, Mexico
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2
FES-ZARAGOZA UNAM, UMIEZ-UIDCC, Mexico
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3
CINVESTAV, Mexico
HPV L1-based virus like particles vaccines (VLPs) are efficient to induce temporary prophylactic activity through the induction of neutralizing antibodies (1). However VLPs that can provide prophylactic as well as therapeutic properties for a long time are necessary. We generated a novel HPV 16 L1-based chimeric virus like particle (cVLP) that was produced in plants and that contains a string of T-cell epitopes from HPV 16 E6 and E7 fused to its C-terminus (2-4). In the present study we analyzed the persistence of specific IgG antibodies with neutralizing activity induced by the immunization with cVLPs, as well as their therapeutic potential in a tumor model of C57BL/6 mice strain. Interestingly, we obtained that these cVLPs induced persistent IgG antibodies for over 12 months, with cross-reactivity and cross-neutralizing activity for VLPs composed of HPV-16 L1 protein. Efficient prevention and rejection of tumors induced by TC-1 tumor cells expressing HPV-16 E6/E7 oncoproteins was observed in mice immunized with these cVLPs. In addition, in mice bearing tumors, important tumor regression (57%) was observed after immunization with cVLPs. The chimeric particles of the type described in this work may potentially be the basis for developing HPV prophylactic and therapeutic vaccines with high efficacy.
Acknowledgements
Support: CONACYT (82827 and 8373); FIS-IMSS/PROT (60 and 617 and 876) grants.
References
1.- Schiller JT, Castellsagué X, Garland SM (2012) A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines. Vaccine 30S:F123-F138.
2.- Paz de la Rosa G, Monroy-García A, Mora-García ML, Hernández-Montes J, Weiss-Steider B, Gómez-Lim MA (2009) An HPV16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice. Virol J 6:2.
3.- Monroy-García A, Hernández-Montes J, Mora-García ML (2007) Identification of epitopes from L1, E6, and E7 proteins of the HPV-16 and 18 types and its implication for diagnosis and treatment of cervical carcinoma. In: Advances in Cancer Research at UNAM (Universidad Nacional Autónoma de México) Manual Moderno, UNAM and PUIS (ed), pp:1-32.
4.- Monroy-García A, Gómez-Lim MA, Weiss-Steider B, la Rosa GP, Hernández-Montes J, Pérez-Saldaña K, Tapia-Guerrero YS, Toledo-Guzmán ME, Santiago-Osorio E, Sanchez-Peña HI, Mora-García Mde L (2011) A novel HPV 16 L1-based chimeric virus-like particle containing E6 and E7 seroreactive epitopes permits highly specific detection of antibodies in patients with CIN 1 and HPV-16 infection. Virol J 8:59.
Keywords:
virus like particles,
HPV vaccine,
tumor rejection,
cervical cancer,
therapeutic efficacy
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Translational immunology and immune intervention
Citation:
MONROY-GARCIA
A,
GOMEZ-LIM
M,
HERNÁNDEZ-MONTES
J,
WEISS-STEIDER
B,
GARCIA-ROCHA
R and
MORA-GARCÍA
M
(2013). A novel HPV-16 L1 based chimeric virus-like particle containing HPV 16 E6 and E7 epitopes elicits a persistent specific antibody immune response and tumor regression..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00654
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Received:
12 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. ALBERTO MONROY-GARCIA, INSTITUTO MEXICANO DEL SEGURO SOCIAL, UIMEO, DISTRITO FEDERAL, México, D.F, 09720, Mexico, albertomon@yahoo.com