scholarly journals Nasal Immunization of Mice with Human Papillomavirus Type 16 (HPV-16) Virus-Like Particles or with the HPV-16 L1 Gene Elicits Specific Cytotoxic T Lymphocytes in Vaginal Draining Lymph Nodes

1999 ◽  
Vol 73 (11) ◽  
pp. 9063-9071 ◽  
Author(s):  
Catherine Dupuy ◽  
Dominique Buzoni-Gatel ◽  
Antoine Touzé ◽  
Daniel Bout ◽  
Pierre Coursaget
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Immune Responses ◽  
Self Assembly ◽  
Genital Tract ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Mammalian Expression ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

ABSTRACT Human papillomavirus type 16 (HPV-16) infects the genital tract and is closely associated with the development of cervical cancer. HPV-16 initiates infection at the genital mucosal surface; thus, mucosal immune responses are likely to contribute to defense against HPV-16 infection. However, little information is available regarding the induction of immune responses in the genital tract mucosa. In this study, we evaluated the potential of intranasally administered papillomavirus vaccines to elicit both systemic and vaginal immune responses. HPV-16 virus-like particles (VLPs) produced by self-assembly of L1 protein and the HPV-16 L1 gene cloned into a mammalian expression vector were used as vaccines. Intranasally administered VLPs induced serum immunoglobulin G (IgG) and vaginal IgA secretory antibodies. Very weak serum IgG and vaginal IgA responses were found after DNA immunization. Both splenic and vaginal lymphocytes could be activated by intranasal immunization with VLPs and the HPV-16 L1 gene. Activated CD4+ Th1-like T cells were shown to synthesize gamma interferon, and activated CD8+ T cells were demonstrated to be cytotoxic.

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

2006 ◽  
Vol 72 (1) ◽  
pp. 745-752 ◽  
Author(s):  
Karina Araujo Aires ◽  
Aurora Marques Cianciarullo ◽  
Sylvia Mendes Carneiro ◽  
Luisa Lina Villa ◽  
Enrique Boccardo ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Lactobacillus Casei ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Human Papillomavirus Type 16 ◽  
Common Causes ◽  
Electron Microscopy Analysis ◽  
Microscopy Analysis ◽  
L1 Protein

ABSTRACT 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.

scholarly journals The L1 Major Capsid Protein of Human Papillomavirus Type 16 Variants Affects Yield of Virus-Like Particles Produced in an Insect Cell Expression System

1998 ◽  
Vol 36 (7) ◽  
pp. 2046-2051 ◽  
Author(s):  
Antoine Touze ◽  
Slimane El Mehdaoui ◽  
Pierre-Yves Sizaret ◽  
Christine Mougin ◽  
Nubia Muñoz ◽  
...  
Keyword(s):  
Amino Acids ◽  
Human Papillomavirus ◽  
Expression System ◽  
The Philippines ◽  
Serological Tests ◽  
Hpv 16 ◽  
Virus Like Particles ◽  
Human Papillomavirus Type 16 ◽  
Amino Acid Region ◽  
L1 Protein

The L1 major capsid proteins of six human papillomavirus type 16 (HPV-16) strains were expressed in insect cells by using recombinant baculoviruses. Virus-like particles (VLPs) which appeared similar to empty virions were identified by electron microscopy for all HPV strains investigated. However, the yield of VLPs produced varied in a range from 1 to 79 depending on the HPV-16 strain. The L1 proteins of these strains differed by up to 15 amino acids from the L1 protein of the prototype HPV-16 strain. Mutations in the amino acid region from residues 83 to 97 seemed to affect the level of expression of the L1 protein. These results are important when considering the development of HPV vaccines and serological tests. They indicate that strains inducing high levels of VLP production must be selected for the development of vaccines. Moreover, the L1 proteins of all strains investigated were able to bind with DNA. We also investigated the seroreactivities of VLPs derived from three different HPV-16 strains from Algeria, Senegal, and the Philippines by testing sera from women from 11 countries in immunoglobulin G-specific enzyme-linked immunosorbent assays. We observed a strong correlation between the reactivities of the three different VLP variants, independent of the geographical origin of the sera investigated. These results indicate that the three strains investigated are serologically cross-reactive despite the fact that their L1 proteins differ in 14 amino acids and suggest that VLPs derived from only one HPV-16 strain could be sufficient for the development of an HPV-16 vaccine and anti-HPV-16 tests.

Efficient self-assembly of human papillomavirus type 16 L1 and L1-L2 into virus-like particles.

1993 ◽  
Vol 67 (12) ◽  
pp. 6929-6936 ◽  
Author(s):  
R Kirnbauer ◽  
J Taub ◽  
H Greenstone ◽  
R Roden ◽  
M Dürst ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Self Assembly ◽  
Virus Like Particles ◽  
Human Papillomavirus Type 16

scholarly journals Expression of Human Papillomavirus Type 16 L1 Protein inEscherichia coli:Denaturation, Renaturation, and Self-Assembly of Virus-like Particlesin Vitro

Virology ◽  
1998 ◽  
Vol 243 (2) ◽  
pp. 423-431 ◽  
Author(s):  
Wei Zhang ◽  
Jeremy Carmichael ◽  
Jackie Ferguson ◽  
Stephen Inglis ◽  
Houman Ashrafian ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Self Assembly ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

scholarly journals Immune Responses and Therapeutic Antitumor Effects of an Experimental DNA Vaccine Encoding Human Papillomavirus Type 16 Oncoproteins Genetically Fused to Herpesvirus Glycoprotein D

2010 ◽  
Vol 17 (10) ◽  
pp. 1576-1583 ◽  
Author(s):  
Mariana O. Diniz ◽  
Marcio O. Lasaro ◽  
Hildegund C. Ertl ◽  
Luís C. S. Ferreira
Keyword(s):  
Human Papillomavirus ◽  
T Cell ◽  
Immune Responses ◽  
Dna Vaccine ◽  
T Cell Responses ◽  
Glycoprotein D ◽  
Antitumor Effects ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Cell Responses

ABSTRACT Recombinant adenovirus or DNA vaccines encoding herpes simplex virus type 1 (HSV-1) glycoprotein D (gD) genetically fused to human papillomavirus type 16 (HPV-16) oncoproteins (E5, E6, and E7) induce antigen-specific CD8+ T-cell responses and confer preventive resistance to transplantable murine tumor cells (TC-1 cells). In the present report, we characterized some previously uncovered aspects concerning the induction of CD8+ T-cell responses and the therapeutic anticancer effects achieved in C57BL/6 mice immunized with pgD-E7E6E5 previously challenged with TC-1 cells. Concerning the characterization of the immune responses elicited in mice vaccinated with pgD-E7E6E5, we determined the effect of the CD4+ T-cell requirement, longevity, and dose-dependent activation on the E7-specific CD8+ T-cell responses. In addition, we determined the priming/boosting properties of pgD-E7E6E5 when used in combination with a recombinant serotype 68 adenovirus (AdC68) vector encoding the same chimeric antigen. Mice challenged with TC-1 cells and then immunized with three doses of pgD-E7E6E5 elicited CD8+ T-cell responses, measured by intracellular gamma interferon (IFN-γ) and CD107a accumulation, to the three HPV-16 oncoproteins and displayed in vivo antigen-specific cytolytic activity, as demonstrated with carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled target cells pulsed with oligopeptides corresponding to the H-2Db -restricted immunodominant epitopes of the E7, E6, or E5 oncoprotein. Up to 70% of the mice challenged with 5 × 105 TC-1 cells and immunized with pgD-E7E6E5 controlled tumor development even after 3 days of tumor cell challenge. In addition, coadministration of pgD-E7E6E5 with DNA vectors encoding pGM-CSF or interleukin-12 (IL-12) enhanced the therapeutic antitumor effects for all mice challenged with TC-1 cells. In conclusion, the present results expand our previous knowledge on the immune modulation properties of the pgD-E7E6E5 vector and demonstrate, for the first time, the strong antitumor effects of the DNA vaccine, raising promising perspectives regarding the development of immunotherapeutic reagents for the control of HPV-16-associated tumors.

A DNA vaccine based on a shuffled E7 oncogene of the human papillomavirus type 16 (HPV 16) induces E7-specific cytotoxic T cells but lacks transforming activity

Vaccine ◽  
2001 ◽  
Vol 19 (30) ◽  
pp. 4276-4286 ◽  
Author(s):  
Wolfram Osen ◽  
Tanja Peiler ◽  
Peter Öhlschläger ◽  
Sandra Caldeira ◽  
Stefan Faath ◽  
...  
Keyword(s):  
T Cells ◽  
Human Papillomavirus ◽  
Dna Vaccine ◽  
Cytotoxic T Cells ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
Transforming Activity ◽  
E7 Oncogene

scholarly journals Influence of Codon Bias on Heterologous Production of Human Papillomavirus Type 16 Major Structural Protein L1 in Yeast

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Milda Norkiene ◽  
Alma Gedvilaite
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Codon Bias ◽  
Heterologous Gene Expression ◽  
Heterologous Production ◽  
Structural Protein ◽  
Hpv 16 ◽  
Major Structural Protein ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein

Heterologous gene expression is dependent on multistep processes involving regulation at the level of transcription, mRNA turnover, protein translation, and posttranslational modifications. Codon bias has a significant influence on protein yields. However, sometimes it is not clear which parameter causes observed differences in heterologous gene expression as codon adaptation typically optimizes many sequence properties at once. In the current study, we evaluated the influence of codon bias on heterologous production of human papillomavirus type 16 (HPV-16) major structural protein L1 in yeast by expressing five variants of codon-modified open reading frames (OFRs) encoding HPV-16 L1 protein. Our results showed that despite the high toleration of various codons used throughout the length of the sequence of heterologously expressed genes in transformed yeast, there was a significant positive correlation between the gene's expression level and the degree of its codon bias towards the favorable codon usage. The HPV-16 L1 protein expression in yeast can be optimized by adjusting codon composition towards the most preferred codon adaptation, and this effect most probably is dependent on the improved translational elongation.

Genetic variability in the major capsid L1 protein of human papillomavirus type 16 (HPV-16) and 18 (HPV-18)

2011 ◽  
Vol 11 (8) ◽  
pp. 2119-2124 ◽  
Author(s):  
E. Frati ◽  
S. Bianchi ◽  
D. Colzani ◽  
A. Zappa ◽  
G. Orlando ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Genetic Variability ◽  
Hpv 16 ◽  
Human Papillomavirus Type 16 ◽  
L1 Protein ◽  
Hpv 18
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