HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7

The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV) is absolute...

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Autores principales: I. S. Malakhov, R. I. Al-Shehadat, I. V. Duckhovlinov, A. S. Simbirtsev
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Publicado: Sankt-Peterburg : NIIÈM imeni Pastera 2017
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spelling oai:doaj.org-article:7741ee2be8934944ab6d405110242e002021-11-22T07:09:48ZHUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E72220-76192313-739810.15789/2220-7619-2016-4-345-352https://doaj.org/article/7741ee2be8934944ab6d405110242e002017-01-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/446https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV) is absolutely necessary for it further evolution, HPV DNA was found in 99.97% cases of disease. Except cervical cancer, HPV cause 85% of rectal cancer, 50% of the vulva, vagina and penis cancers, 20% of oropharyngeal cancer and 10% of larynx and esophagus cancers. In 2009, 14 000 women were diagnosed with cervical cancer in Russia. The growth in morbidity was 19% (in comparison with 1999). The most effective recognised measure for almost each infection prophylaxis is a vaccination. Two human papilloma virus vaccines are available in Russia nowadays — Gardasil and Cervarix, produced in Belgium and the Netherlands respectively. Cervarix is a bivalent vaccine based on virus-like particles (VLP) of two types. Recombinant major capsid proteins L1 HPV 16 and HPV 18 express in baculovirus expression system and self-assembled into virus-like particles (about 70 percent of cervical cancers are caused by HPV 16 and HPV 18). VLP of each strain produced in different baculovirus vectors and then combined in single drug. Gardasil is like Cervarix with few exceptions. Producing organisms are fungi S. cerevisiae in this case, and this vaccine contains low-risk HPV 6 and HPV 11 VLP. Thus, Gardasil is quadrivalent HPV-6/11/16/18 vaccine. These vaccines are very effective in averting infection of disease and don’t have significant side-effects, however they have some disadvantages. Firstly, they have a high price because of necessity of their expression in eukaryotic cells. Secondly, they are strain-specific, so vaccines are completely effective only for virus’s strains which are represented in the vaccine. Thirdly, it`s the absence of therapeutic (treatment of established infection) value of stated vaccines. According to information from literature, N-terminus of the L2 protein can induce non strain-specific neutralizing antibody that protects organism from papillomavirus challenge. E7 protein is a virus oncogene, its function is unlimited proliferation of infected cells that cause malignization in chronic course of disease. This protein is a very attractive target for therapeutic vaccines because of its necessity both for virus life cycle and sustenance of malignant phenotype in cancer cells. So, in this research the design of immunogen on the base of proteins HPV L2 and E7 is selected, vaccine on the base of which will avoid the disadvantages of Gardasil and Cervarix listed above. The stain-producer of protein on the base of cells E. coli was created. The protein was purified in denaturing reducing conditions by metal-affine chromatography and refold by sequential remove of urea and 2-mercaptoethanol.I. S. MalakhovR. I. Al-ShehadatI. V. DuckhovlinovA. S. SimbirtsevSankt-Peterburg : NIIÈM imeni Pasteraarticlehpv vaccinepapillomahuman papillomavirusl2 proteine7 proteinfoldingInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 6, Iss 4, Pp 345-352 (2017)
institution DOAJ
collection DOAJ
language RU
topic hpv vaccine
papilloma
human papillomavirus
l2 protein
e7 protein
folding
Infectious and parasitic diseases
RC109-216
spellingShingle hpv vaccine
papilloma
human papillomavirus
l2 protein
e7 protein
folding
Infectious and parasitic diseases
RC109-216
I. S. Malakhov
R. I. Al-Shehadat
I. V. Duckhovlinov
A. S. Simbirtsev
HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
description The cervical cancer is one of the most common diseases in world. This malignancy is the seventh highest prevalence oncological disease worldwide and the second highest prevalence oncological disease of women in the world. Meanwhile women need to be infected by human papilloma virus (HPV) is absolutely necessary for it further evolution, HPV DNA was found in 99.97% cases of disease. Except cervical cancer, HPV cause 85% of rectal cancer, 50% of the vulva, vagina and penis cancers, 20% of oropharyngeal cancer and 10% of larynx and esophagus cancers. In 2009, 14 000 women were diagnosed with cervical cancer in Russia. The growth in morbidity was 19% (in comparison with 1999). The most effective recognised measure for almost each infection prophylaxis is a vaccination. Two human papilloma virus vaccines are available in Russia nowadays — Gardasil and Cervarix, produced in Belgium and the Netherlands respectively. Cervarix is a bivalent vaccine based on virus-like particles (VLP) of two types. Recombinant major capsid proteins L1 HPV 16 and HPV 18 express in baculovirus expression system and self-assembled into virus-like particles (about 70 percent of cervical cancers are caused by HPV 16 and HPV 18). VLP of each strain produced in different baculovirus vectors and then combined in single drug. Gardasil is like Cervarix with few exceptions. Producing organisms are fungi S. cerevisiae in this case, and this vaccine contains low-risk HPV 6 and HPV 11 VLP. Thus, Gardasil is quadrivalent HPV-6/11/16/18 vaccine. These vaccines are very effective in averting infection of disease and don’t have significant side-effects, however they have some disadvantages. Firstly, they have a high price because of necessity of their expression in eukaryotic cells. Secondly, they are strain-specific, so vaccines are completely effective only for virus’s strains which are represented in the vaccine. Thirdly, it`s the absence of therapeutic (treatment of established infection) value of stated vaccines. According to information from literature, N-terminus of the L2 protein can induce non strain-specific neutralizing antibody that protects organism from papillomavirus challenge. E7 protein is a virus oncogene, its function is unlimited proliferation of infected cells that cause malignization in chronic course of disease. This protein is a very attractive target for therapeutic vaccines because of its necessity both for virus life cycle and sustenance of malignant phenotype in cancer cells. So, in this research the design of immunogen on the base of proteins HPV L2 and E7 is selected, vaccine on the base of which will avoid the disadvantages of Gardasil and Cervarix listed above. The stain-producer of protein on the base of cells E. coli was created. The protein was purified in denaturing reducing conditions by metal-affine chromatography and refold by sequential remove of urea and 2-mercaptoethanol.
format article
author I. S. Malakhov
R. I. Al-Shehadat
I. V. Duckhovlinov
A. S. Simbirtsev
author_facet I. S. Malakhov
R. I. Al-Shehadat
I. V. Duckhovlinov
A. S. Simbirtsev
author_sort I. S. Malakhov
title HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
title_short HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
title_full HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
title_fullStr HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
title_full_unstemmed HUMAN PAPILLOMA VIRUS IMMUNOGEN CREATION ON THE BASE OF CHIMERIC RECOMBINANT PROTEIN L2E7
title_sort human papilloma virus immunogen creation on the base of chimeric recombinant protein l2e7
publisher Sankt-Peterburg : NIIÈM imeni Pastera
publishDate 2017
url https://doaj.org/article/7741ee2be8934944ab6d405110242e00
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