scholarly journals Obtaining a Vaccine Candidate Against Tumors Expressing the E7 Antigen of Human Papillomavirus type 18

Author(s):  
Nadia Rodríguez Rodríguez ◽  
Alain B Alfonso Chaviano ◽  
Milaid Granadillo Rodríguez ◽  
Aileen Batte Figueredo ◽  
Isis del Carmen Torréns Madrazo

Abstract Background: Cervical cancer is the fourth most common cancer in women worldwide and was the leading cause of death among approximately 300 000 cases in 2018. The main risk factor for developing this disease is the persistent infection of high-risk types of human papillomavirus (HPV); specifically HPV-18 is recognized as one of the major contributors for adenocarcinoma and squamous cancer. There are three prophylactic vaccines to prevent infection by HPV, but these vaccines are not effective in infected people. On the other hand, despite the success of various types of therapeutic vaccine candidates in clinical trials, none of them is commercially available to treat women with HPV-related malignancies. As the methods used for obtaining those therapeutic candidates are awfully expensive, they could be inaccessible for developing countries. In this scenario, E7 antigen of HPV is considered and ideal target for developing therapeutic vaccines. In accordance with this, the aim of this work is to obtain a vaccine candidate with high levels of purity through a profitable process, for treating tumors expressing the E7 antigen of HPV-18.Results: We have obtained the novel therapeutic vaccine candidate CIGB550-E718 that comprises the fusion between an E7 mutein of HPV-18 and the cell-penetrating peptide with immunostimulatory properties CIGB550. The expression of the fusion protein evaluated using two strains of E. coli and 16 culture media with different composition enabled us to choose the best setting in which the interest protein accounted for approximately 16% of the total cellular protein. The best results were obtained using BL21(DE3) cells as host system grown in a culture medium containing M9 salt, casein hydrolysate and glycerol as a carbon source. The recombinant protein was purified by a single affinity chromatographic step up to 90% purity. Yields of 32 mg of the CIGB550-E718 per liter of culture were achieved from 2.5 L scale.Conclusions: These results are a promising and cost-effective approach for the future production and scale-up of the protein CIGB550-E718, which could be a therapeutic alternative for treating women with lesions associated to HPV-18 infection.

Vaccine ◽  
2019 ◽  
Vol 37 (30) ◽  
pp. 3957-3960 ◽  
Author(s):  
Milaid Granadillo ◽  
Aileen Batte ◽  
Alain B. Alfonso ◽  
Aracelys Blanco ◽  
Dioslaida Urquiza ◽  
...  

PLoS ONE ◽  
2017 ◽  
Vol 12 (8) ◽  
pp. e0183177 ◽  
Author(s):  
Romana J. R. Yanez ◽  
Renate Lamprecht ◽  
Milaid Granadillo ◽  
Brandon Weber ◽  
Isis Torrens ◽  
...  

Author(s):  
N.A. Shmakova ◽  
G.N. Chistyakova ◽  
I.N. Kononova ◽  
I.I. Remizova

Recently, there has been a steady growth of cervical cancer all over the world, especially in Russia. Patients with cervical cancer have become much younger. At the same time, the human papillomavirus is not only the main factor in the neoplastic process, but it is also one of the most common sexually transmitted infections in the world. The aim of the paper is to assess the prevalence and characteristics of human papillomavirus genotypes in patients with cervical intraepithelial neoplasia. Materials and Methods. During the periodic screening we examined 213 women of a reproductive age with HPV infection. All patients underwent liquid-based cytology and human papillomavirus genotyping by polymerase chain reaction. Results. We revealed that the prevalence of cervical intraepithelial neoplasia among women with papillomavirus infection was 80.3 % (n=171). According to human papillomavirus genotyping, HPV 16 (38 %) and HPV 33 (32 %) prevailed. We also observed positive high correlation between high-grade squamous intraepithelial lesions (HSIL) and HPV 18 (r=+0.759, p=0.001), a negative mean correlation between HPV 45 and low-grade squamous intraepithelial lesions (LSIL) (r=-0.643, p=0.002). A cohort of patients with severe intraepithelial cervical lesions demonstrated high viral load rates. Conclusion. According to the results obtained, we established the dominance of HPV 16 and HPV 33 genotypes in cervical intraepithelial neoplasia. There were significant differences between HSIL and LSIL patients with HPV 18 and HPV 45. There was also a correlation between an increase in the viral load with the severity of the pathological process. Keywords: human papillomavirus, intraepithelial cervical neoplasms, cervical cancer. В последние годы в мире, особенно в России, наблюдается неуклонный рост и «омолаживание» рака шейки матки. При этом вирус папилломы человека является не только основным фактором прогрессирования неопластического процесса, но и одной из наиболее распространенных инфекций, предаваемых половым путем, в мире. Цель. Оценить распространенность и характеристику генотипов папилломавирусной инфекции у пациенток с цервикальными интраэпителиальными неоплазиями. Материалы и методы. Проведено обследование 213 пациенток репродуктивного возраста с ВПЧ-инфекцией, пришедших на профилактический осмотр. Всем женщинам было выполнено цитологическое исследование жидкостным методом и генотипирование вируса папилломы человека методом полимеразной цепной реакции. Результаты. Распространенность цервикальных интраэпителиальных неоплазий среди женщин с папилломавирусной инфекцией составила 80,3 % (171 пациентка). Согласно данным генотипирования вируса папилломы человека превалировал 16-й (38 %) и 33-й типы (32 %). Выявлена положительная высокая корреляционная связь между цервикальными неоплазиями высокой степени онкогенного риска (HSIL) и 18-м типом ВПЧ-инфекции (r=+0,759 при р=0,001), отрицательная средняя корреляционная связь 45-го типа ВПЧ с низкой степенью онкогенного риска (LSIL) (r=-0,643 при р=0,002). Продемонстрированы высокие показатели вирусной нагрузки в когорте пациенток с тяжелыми внутриэпителиальными цервикальными поражениями. Выводы. По результатам полученных данных установлено доминирование 16-го и 33-го генотипов ВПЧ при цервикальных интраэпителиальных неоплазиях с наличием значимых различий между пациентами с HSIL и LSIL в отношении 18-го и 45-го типов, а также связь роста уровня вирусной нагрузки с увеличением степени тяжести патологического процесса. Ключевые слова: вирус папилломы человека, интраэпителиальные новообразования шейки матки, рак шейки матки.


Vaccines ◽  
2014 ◽  
Vol 2 (2) ◽  
pp. 422-462 ◽  
Author(s):  
Hadeel Khallouf ◽  
Agnieszka Grabowska ◽  
Angelika Riemer

2019 ◽  
Vol 4 (2) ◽  
pp. 252-262
Author(s):  
Yani Suryani ◽  
Opik Taupiqurrohman ◽  
Muhammad Yusuf ◽  
Toto Subroto ◽  
Sukma Nuswantara

 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 


Genetika ◽  
2006 ◽  
Vol 38 (2) ◽  
pp. 129-136
Author(s):  
Velichka Rodeva ◽  
Stanislava Grozeva ◽  
Velichka Todorova

Callusogenesis and regeneration ability of cotyledon and hypocotyl explants from three Bulgarian pepper varieties in MS basal medium supplemented with l-3mg/l BAP. l.0mg/1 IAA and 0.5mg/l GA3 was studied. In the different variants of culture medium was registered high level of callusogenesis and organogenesis in both type of explants from the all varieties. The highest percentage of plant-regenerants is established in cotyledon explants (from 3.3 to 18.3) in variant 3 of the culture medium containing 3mg/l BA. In the process of micropropagation by stem explants of the same studied pepper varieties the addition of the vitamins C. B12. Casein hydrolysate and Ferulic acid had a stimulation effect on the plant growth in height and rooting. In result of anther cultivation from three pepper varieties and four breeding lines the highest percentage of embryo structure formation was registered in varieties Albena and Strjama (12.0 and 13.8 respectively). The Bulgarian peppers are recalcitrant and their in vitro answer is different depending from the explants type, genotype and the culture media composition.


2016 ◽  
Vol 3 (8) ◽  
pp. 64-68
Author(s):  
M Mashhadi Abolghasem Shirazi ◽  
F Roohvand ◽  
A Arashkia ◽  
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