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Papillomavirus pseudovirions packaged with the L2 gene induce cross-neutralizing antibodies.

Abstract : BACKGROUND: Current vaccines against HPVs are constituted of L1 protein self-assembled into virus-like particles (VLPs) and they have been shown to protect against natural HPV16 and HPV18 infections and associated lesions. In addition, limited cross-protection has been observed against closely related types. Immunization with L2 protein in animal models has been shown to provide cross-protection against distant papillomavirus types, suggesting that the L2 protein contains cross-neutralizing epitopes. However, vaccination with L2 protein or L2 peptides does not induce high titers of anti-L2 antibodies. In order to develop a vaccine with the potential to protect against other high-risk HPV types, we have produced HPV58 pseudovirions encoding the HPV31 L2 protein and compared their capacity to induce cross-neutralizing antibodies with that of HPV L1 and HPV L1/L2 VLPs. METHODS: The titers of neutralizing antibodies against HPV16, HPV18, HPV31 and HPV58 induced in Balb/c mice were compared after immunization with L2-containing vaccines. RESULTS: Low titers of cross-neutralizing antibodies were detected in mice when immunized with L1/L2 VLPs, and the highest levels of cross-neutralizing antibodies were observed in mice immunized with HPV 58 L1/L2 pseudovirions encoding the HPV 31 L2 protein. CONCLUSIONS: The results obtained indicate that high levels of cross-neutralizing antibodies are only observed after immunization with pseudovirions encoding the L2 protein. HPV pseudovirions thus represent a possible new strategy for the generation of a broad-spectrum vaccine to protect against high-risk HPVs and associated neoplasia.
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Submitted on : Friday, January 27, 2012 - 2:23:55 PM
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Nicolas Combelas, Emilie Saussereau, Maxime Fleury, Tatiana Ribeiro, Julien Gaitan, et al.. Papillomavirus pseudovirions packaged with the L2 gene induce cross-neutralizing antibodies.. Journal of Translational Medicine, BioMed Central, 2010, 8 (1), pp.28. ⟨10.1186/1479-5876-8-28⟩. ⟨inserm-00663763⟩



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