Production of human papillomavirus type 16 L1 virus-like particles by recombinant Lactobacillus casei cells.
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.
Aires
Karina Araujo
KA
Centro de Biotecnologia, Instituto Butantan, São Paulo, Brazil.
Cianciarullo
Aurora Marques
AM
Carneiro
Sylvia Mendes
SM
Villa
Luisa Lina
LL
Boccardo
Enrique
E
Pérez-Martinez
Gaspar
G
Perez-Arellano
Isabel
I
Oliveira
Maria Leonor Sarno
ML
Ho
Paulo Lee
PL
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D036022:Capsid Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D052162:Human papillomavirus 16 / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007780:Lacticaseibacillus casei / Q000235:genetics / Q000378:metabolism*; D007785:Lactose / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009856:Oncogene Proteins, Viral / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009876:Operon; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D011995:Recombination, Genetic; D018411:Spodoptera; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014771:Virion / Q000378:metabolism*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D009856:Oncogene Proteins, Viral; D014765:Viral Vaccines; C063317:L1 protein, Human papillomavirus type 16; D007785:Lactose