Computational Modeling of Immune Response Triggering Immunogenic Peptide Vaccine Against the Human Papillomaviruses to Induce Immunity Against Cervical Cancer

2021 ◽  
Author(s):  
Namra Ahmad ◽  
Syed Shujait Ali ◽  
Sajjad Ahmad ◽  
Zahid Hussain ◽  
Muhammad Qasim ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Immune Response ◽  
Computational Modeling ◽  
Peptide Vaccine ◽  
Human Papillomaviruses ◽  
Immunogenic Peptide

scholarly journals Adenoviral Vectors Armed with PAPILLOMAVIRUs Oncogene Specific CRISPR/Cas9 Kill Human-Papillomavirus-Induced Cervical Cancer Cells

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1934 ◽  
Author(s):  
Eric Ehrke-Schulz ◽  
Sonja Heinemann ◽  
Lukas Schulte ◽  
Maren Schiwon ◽  
Anja Ehrhardt
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Adenoviral Vectors ◽  
Human Papillomaviruses ◽  
Cervical Cancer Cell ◽  
Adenoviral Delivery ◽  
Cervical Cancer Cells

Human papillomaviruses (HPV) cause malignant epithelial cancers including cervical carcinoma, non-melanoma skin and head and neck cancer. They drive tumor development through the expression of their oncoproteins E6 and E7. Designer nucleases were shown to be efficient to specifically destroy HPV16 and HPV18 oncogenes to induce cell cycle arrest and apoptosis. Here, we used high-capacity adenoviral vectors (HCAdVs) expressing the complete CRISPR/Cas9 machinery specific for HPV18-E6 or HPV16-E6. Cervical cancer cell lines SiHa and CaSki containing HPV16 and HeLa cells containing HPV18 genomes integrated into the cellular genome, as well as HPV-negative cancer cells were transduced with HPV-type-specific CRISPR-HCAdV. Upon adenoviral delivery, the expression of HPV-type-specific CRISPR/Cas9 resulted in decreased cell viability of HPV-positive cervical cancer cell lines, whereas HPV-negative cells were unaffected. Transduced cervical cancer cells showed increased apoptosis induction and decreased proliferation compared to untreated or HPV negative control cells. This suggests that HCAdV can serve as HPV-specific cancer gene therapeutic agents when armed with HPV-type-specific CRISPR/Cas9. Based on the versatility of the CRISPR/Cas9 system, we anticipate that our approach can contribute to personalized treatment options specific for the respective HPV type present in each individual tumor.

scholarly journals HPV and Other Microbiota; Who’s Good and Who’s Bad: Effects of the Microbial Environment on the Development of Cervical Cancer—A Non-Systematic Review

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 714
Author(s):  
Matthias Läsche ◽  
Horst Urban ◽  
Julia Gallwas ◽  
Carsten Gründker
Keyword(s):  
Systematic Review ◽  
Cervical Cancer ◽  
High Risk ◽  
Cervical Carcinoma ◽  
Hpv Infection ◽  
Human Papillomaviruses ◽  
Inflammatory Reactions ◽  
Metabolic Signalling ◽  
Microbial Environment ◽  
High Risk Hpv

Cervical cancer is responsible for around 5% of all human cancers worldwide. It develops almost exclusively from an unsolved, persistent infection of the squamocolumnar transformation zone between the endo- and ecto-cervix with various high-risk (HR) human papillomaviruses (HPVs). The decisive turning point on the way to persistent HPV infection and malignant transformation is an immune system weakened by pathobionts and oxidative stress and an injury to the cervical mucosa, often caused by sexual activities. Through these injury and healing processes, HPV viruses, hijacking activated keratinocytes, move into the basal layers of the cervical epithelium and then continue their development towards the distal prickle cell layer (Stratum spinosum). The microbial microenvironment of the cervical tissue determines the tissue homeostasis and the integrity of the protective mucous layer through the maintenance of a healthy immune and metabolic signalling. Pathological microorganisms and the resulting dysbiosis disturb this signalling. Thus, pathological inflammatory reactions occur, which manifest the HPV infection. About 90% of all women contract an HPV infection in the course of their lives. In about 10% of cases, the virus persists and cervical intra-epithelial neoplasia (CIN) develops. Approximately 1% of women with a high-risk HPV infection incur a cervical carcinoma after 10 to 20 years. In this non-systematic review article, we summarise how the sexually and microbial mediated pathogenesis of the cervix proceeds through aberrant immune and metabolism signalling via CIN to cervical carcinoma. We show how both the virus and the cancer benefit from the same changes in the immune and metabolic environment.

scholarly journals Human papillomavirus E7 oncoprotein targets RNF168 to hijack the host DNA damage response

2019 ◽  
Vol 116 (39) ◽  
pp. 19552-19562 ◽  
Author(s):  
Justine Sitz ◽  
Sophie Anne Blanchet ◽  
Steven F. Gameiro ◽  
Elise Biquand ◽  
Tia M. Morgan ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Dna Damage ◽  
Cancer Cells ◽  
Genomic Instability ◽  
E3 Ligase ◽  
Human Papillomaviruses ◽  
Double Strand Breaks ◽  
Nuclear Bodies ◽  
Dna Double Strand Breaks ◽  
Strand Breaks

High-risk human papillomaviruses (HR-HPVs) promote cervical cancer as well as a subset of anogenital and head and neck cancers. Due to their limited coding capacity, HPVs hijack the host cell’s DNA replication and repair machineries to replicate their own genomes. How this host–pathogen interaction contributes to genomic instability is unknown. Here, we report that HPV-infected cancer cells express high levels of RNF168, an E3 ubiquitin ligase that is critical for proper DNA repair following DNA double-strand breaks, and accumulate high numbers of 53BP1 nuclear bodies, a marker of genomic instability induced by replication stress. We describe a mechanism by which HPV E7 subverts the function of RNF168 at DNA double-strand breaks, providing a rationale for increased homology-directed recombination in E6/E7-expressing cervical cancer cells. By targeting a new regulatory domain of RNF168, E7 binds directly to the E3 ligase without affecting its enzymatic activity. As RNF168 knockdown impairs viral genome amplification in differentiated keratinocytes, we propose that E7 hijacks the E3 ligase to promote the viral replicative cycle. This study reveals a mechanism by which tumor viruses reshape the cellular response to DNA damage by manipulating RNF168-dependent ubiquitin signaling. Importantly, our findings reveal a pathway by which HPV may promote the genomic instability that drives oncogenesis.

scholarly journals Immunoinformatics Study on Early 4 Protein of Human Papillomavirus Type 16 for Cervical Cancer Vaccine Peptide Candidate

2019 ◽  
Vol 4 (2) ◽  
pp. 252-262
Author(s):  
Yani Suryani ◽  
Opik Taupiqurrohman ◽  
Muhammad Yusuf ◽  
Toto Subroto ◽  
Sukma Nuswantara
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
Amino Acid ◽  
Cancer Vaccine ◽  
Vaccine Candidate ◽  
Peptide Vaccine ◽  
Human Papillomavirus Type 16 ◽  
Cervical Cancer Vaccine ◽  
Peptide Candidate

 The aims of this study were to carry out testing of the early 4 protein of type 16 HPV through immunoinformatics meth-ods in an effort to get the peptide vaccine candidate for cervical cancer. The software used are IEDB-AR, CABSdock and Accelrys Discovery Study 4.5. Based on the analysis that sequence of ami-no acid lysine, leucine, leucine, glycine, serine, threonine, tryp-tophan, proline and threonine (KLLGSTWPT) and the sequence of amino acid tyrosine, tyrosine, valine, leucine, histidine, leucine, cysteine, leucine, alanine, alanine, threonine, lysine, tyrosine, pro-line and leucine (YYVLHLCLAATKYPL) are peptide vaccine can-didate for cervical cancer from the early 4 protein of HPV type 16 

scholarly journals Antibodies against Early Proteins of Human Papillomaviruses as Diagnostic Markers for Invasive Cervical Cancer

1998 ◽  
Vol 36 (2) ◽  
pp. 475-480 ◽  
Author(s):  
Wolfgang Meschede ◽  
Klaus Zumbach ◽  
Joris Braspenning ◽  
Martin Scheffner ◽  
Luis Benitez-Bribiesca ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Invasive Cervical Cancer ◽  
Human Papillomaviruses ◽  
Antibody Detection ◽  
Diagnostic Tools ◽  
Immunological Monitoring ◽  
Hpv Dna ◽  
Native Proteins ◽  
Human Sera ◽  
E6 And E7

Cervical cancer is the most prevalent tumor in developing countries and the second most frequent cancer among females worldwide. Specific human papillomaviruses (HPVs) and, most notably, HPV types 16 and 18 are recognized as being causally associated with this malignancy. Antibodies against early HPV proteins E6 and E7 have been found more often in patients with tumors than in controls. Existing peptide enzyme-linked immunosorbent assays (ELISAs) for the detection of anti-E6 and anti-E7 antibodies in human sera have low levels of sensitivity and specificity and thus are not suitable for use as diagnostic tools. Based on highly purified recombinant native proteins, we developed four sandwich ELISAs for the detection of antibodies against HPV type 16 and 18 E6 and E7 proteins. We demonstrate their sensitivities and high degrees of specificity for cervical cancer. Among a total of 501 serum specimens from unselected patients with invasive cervical cancer, 52.9% reacted positively in at least one of the four assays. In contrast, among 244 serum specimens from control subjects without cervical cancer, only 2 reactive serum specimens (0.8%) were found. For 19 of 19 antibody-positive patients, the HPV type indicated by seroreactivity was identical to the HPV DNA type found in the tumor, which also indicates a high degree of specificity for antibody detection with respect to HPV type. In a direct comparison of 72 serum specimens from patients with cervical cancer, 56% of the specimens reacted in at least one of the four protein ELISAs, whereas 40% reacted in at least one of seven peptide ELISAs covering the four antigens. These assays could be of value for the detection of invasive cervical cancer in settings in which cytology-based early tumor screening is not available, for the clinical management of patients diagnosed with cervical cancer, and for the immunological monitoring of E6 and E7 vaccination trials.

scholarly journals Detection of human papillomavirus type 16 oncogen E7 in surgical materials from Russian prostate cancer patients

2017 ◽  
Vol 16 (3) ◽  
pp. 59-62 ◽  
Author(s):  
G. M. Volgareva ◽  
V. D. Ermilova ◽  
A. V. Khachaturyan ◽  
V. V. Tatarskiy ◽  
L. S. Pavlova
Keyword(s):  
Prostate Cancer ◽  
Cervical Cancer ◽  
High Speed ◽  
Human Papillomaviruses ◽  
Chain Reaction ◽  
Dna Preservation ◽  
Human Papillomavirus Type 16 ◽  
Incidence And Mortality ◽  
Polymerase Chain ◽  
E7 Oncogene

Introduction. High indices of prostate cancer (PC) incidence and mortality as well as high speed of growth of these figures testify to urgency of research into PC origin as well as means of its prophylaxis. The problem of possible PC association with oncogenic human papillomaviruses (HPV) is still being disputable. Objective: to test whether surgical materials from PC patients in Russia harbour E7 oncogene of HPV type 16 (HPV16), the main HPV type responsible for cervical cancer. Materials and methods. Prostate tissues excised in the course of radical prostatectomy from 17 PC patients were tested by polymerase chain reaction. For better DNA preservation cryopreserved tumor specimens not treated with either formalin or paraffin were used. The PC typical multifocal type of growth was taken into account by microdissecting of cryostate cuts to accumulate homogeneous cells (cancerous, dysplastic or normal). Results. HPV16 E7 was registered in prostate tissues of 7 patients out of 17 examined including all those 5 cases for which DNA had been isolated from homogeneous sites of cancer cells. Conclusion. The result obtained enables one to admit that HPV16 may be harbored in prostates of Russian PC patients not infrequently.

scholarly journals Acceptability and feasibility of human papillomavirus vaccination for adolescents in school environments in Libreville

2020 ◽  
Vol 9 (9) ◽  
pp. 3541
Author(s):  
Nathalie L. Ambounda ◽  
Sylvain H. Woromogo ◽  
Olive M. Kenmogne ◽  
Felicite E. Yagata Moussa ◽  
Vicky N. Simo Tekem ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Human Papillomavirus ◽  
High Risk ◽  
Precancerous Lesions ◽  
Hpv Vaccination ◽  
Immunization Coverage ◽  
Human Papillomaviruses ◽  
Professional Status ◽  
Human Papillomavirus Vaccination ◽  
Cross Sectional

Background: High-risk oncogenic human papillomaviruses (HPV) are the cause of sexually transmitted viral infection. Its persistence is a risk factor for precancerous lesions of the cervix, which will constitute the base of cervical cancer. In the world, the prevalence of high-risk oncogenic HPV is 66.7%, which is higher among women starting their sexual activity.Methods: An analytical cross-sectional study was conducted in high schools in Gabon regarding parents. The variables selected were the socio-cultural and demographic characteristics of the parents, their knowledge of human papillomavirus vaccination and their acceptability of HPV vaccination and finally the feasibility of HPV vaccination. The statistical test used was Pearson's Chi-square, and a difference was considered significant for p<0.05.Results: The majority of parents, 89%, were informed of the existence of cervical cancer. However, 73.4% of them were unaware of the existence of vaccination against cervical cancer. Only 2.4% of parents had vaccinated their daughters against cervical cancer at the time of the study. These parents only 53.4% expressed an interest in vaccinating their daughters in 53.4% of cases. The ability to vaccinate children is associated with the socio-professional status of parents (p˂0.000).Conclusions: The majority of parents approved school-based vaccination against human papillomavirus infections despite its reported cost and lack of information. The integration of anti-HPV vaccination into the expanded programme on immunization in Gabon will improve immunization coverage.

scholarly journals Computational modeling of the immune response to yellow fever

2016 ◽  
Vol 295 ◽  
pp. 127-138 ◽  
Author(s):  
C.R.B. Bonin ◽  
R.W. dos Santos ◽  
G.C. Fernandes ◽  
M. Lobosco
Keyword(s):  
Immune Response ◽  
Computational Modeling ◽  
Yellow Fever
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