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Applied and Environmental Microbiology, January 2006, p. 745-752, Vol. 72, No. 1
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.1.745-752.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Production of Human Papillomavirus Type 16 L1 Virus-Like Particles by Recombinant Lactobacillus casei Cells

Karina Araujo Aires,1,4 Aurora Marques Cianciarullo,2 Sylvia Mendes Carneiro,3 Luisa Lina Villa,5 Enrique Boccardo,5 Gaspar Pérez-Martinez,6 Isabel Perez-Arellano,7 Maria Leonor Sarno Oliveira,1* and Paulo Lee Ho1,4,8*

Centro de Biotecnologia,1 Laboratório de Genética,2 Laboratório de Biologia Celular, Instituto Butantan, São Paulo, Brazil,3 Interunidades em Biotecnologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil,4 Instituto Ludwig de Pesquisa sobre o Câncer, São Paulo, Brazil,5 Instituto de Agroquímica y Tecnologia de Alimentos,6 Instituto de Investigaciones Citológicas, Valencia, Spain,7 Instituto de Biociências e Instituto de Química, Universidade de São Paulo, São Paulo, Brazil8

Received 1 June 2005/ Accepted 22 September 2005

Infections with human papillomavirus type 16 (HPV-16) are closely associated with the development of human cervical carcinoma, which is one of the most common causes of cancer death in women worldwide. At present, the most promising vaccine against HPV-16 infection is based on the L1 major capsid protein, which self-assembles in virus-like particles (VLPs). In this work, we used a lactose-inducible system based on the Lactobacillus casei lactose operon promoter (plac) for expression of the HPV-16 L1 protein in L. casei. Expression was confirmed by Western blotting, and an electron microscopy analysis of L. casei expressing L1 showed that the protein was able to self-assemble into VLPs intracellularly. The presence of conformational epitopes on the L. casei-produced VLPs was confirmed by immunofluorescence using the anti-HPV-16 VLP conformational antibody H16.V5. Moreover, sera from mice that were subcutaneously immunized with L. casei expressing L1 reacted with Spodoptera frugiperda-produced HPV-16 L1 VLPs, as determined by an enzyme-linked immunosorbent assay. The production of L1 VLPs by Lactobacillus opens the possibility for development of new live mucosal prophylactic vaccines.

* Corresponding author. Mailing address: Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil. Phone: 55 (11) 3726-7222, ext. 2244. Fax: 55 (11) 3726-1505. E-mail address for Paulo Lee Ho: hoplee{at}butantan.gov.br. E-mail address for Maria Leonor Sarno Oliveira: mloliveira{at}butantan.gov.br

Applied and Environmental Microbiology, January 2006, p. 745-752, Vol. 72, No. 1
0099-2240/06/$08.00+0     doi:10.1128/AEM.72.1.745-752.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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  • Ingham, C. J., Beerthuyzen, M., van Hylckama Vlieg, J. (2008). Population Heterogeneity of Lactobacillus plantarum WCFS1 Microcolonies in Response to and Recovery from Acid Stress. Appl. Environ. Microbiol. 74: 7750-7758 [Abstract] [Full Text]  


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