Emerging human papillomavirus vaccines

Ma, Barbara; Maraj, Bharat; Tran, Ngoc Nguyen; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D.; Hung, Chien Fu; Wu, T. C.

doi:10.1517/14728214.2012.744393

Cited by 72 publications

(88 citation statements)

References 157 publications

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“…Estima-se que o HPV esteja envolvido em 5,2% de todos os casos de cânceres mundiais (MA et al, 2012;STANLEY, 2012a). Representa o terceiro tipo de neoplasia mais comum, após o câncer de mama e câncer colorretal, além de ser a quarta principal causa de morte por neoplasia em mulheres no mundo (ROMANOWSKY, 2011).…”

Section: Epidemiologiaunclassified

“…Representa o terceiro tipo de neoplasia mais comum, após o câncer de mama e câncer colorretal, além de ser a quarta principal causa de morte por neoplasia em mulheres no mundo (ROMANOWSKY, 2011). Atualmente representa um importante desafio para a saúde pública mundial, principalmente nos países em desenvolvimento, onde ocorrem mais de 85% de todos os casos de mortes por neoplasia cervical e estima-se para o ano de 2020, o aumento para 90% dos casos (MA et al, 2012). A incidência é cerca de duas vezes maior em países menos desenvolvidos, em relação aos países mais desenvolvidos (INCA, 2012).…”

Section: Epidemiologiaunclassified

“…As proteínas E6 e E7 são importantes na transformação e malignidade celular, regulando o ciclo viral na célula. As oncoproteínas E6 e E7 associam-se aos fatores supressores de tumor presentes na célula, onde a E6 associa-se a níveis celulares de p53 e a E7 atua na proteína retinoblastoma (pRB) (KAVATI, 2012;MA et al, 2012).…”

Section: Genoma Viral E Proteínas Do Papilomavírusunclassified

“…Como a E2 é uma repressora da transcrição dos genes E6 e E7, a perda de E2 permite a desregulação dos oncogenes E6 e E7. As oncoproteínas E6 e E7 inativam e degradam o supressor tumoral p53 e a retinoblastoma (Rb), respectivamente, e ambos os efeitos conduzem à desregulação do ciclo celular, instabilidade genômica e descontrole da proliferação celular (MA et al, 2012;RODEN, 2013b). …”

Section: Ciclo Viralunclassified

“…As neoplasias intraepiteliais de baixo grau (NIC 1) são caracterizadas pelo baixo nível de proliferação celular, geralmente apresentam o genoma viral epissomal, e na maioria das lesões regride espontaneamente. As lesões intraepiteliais de alto grau (NIC 2 e NIC 3) apresentam elevada proliferação viral, geralmente associadas a integração do genoma viral, podendo progredir para o câncer invasivo (FRAZER; LEGATT; MATAROLLO, 2011;MA et al, 2012;STANLEY, 2008). Apropriadas intervenções, geralmente podem prevenir a progressão para o carcinoma invasivo, no entanto existe uma considerável morbidade associada ao tratamento de estágios pré-cancerosos (CUBIE, 2013).…”

Section: Introductionunclassified

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Potencial vacinal de proteínas recombinantes do capsídeo de papilomavírus humano.

Sakauchi¹

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Section: Epidemiologiaunclassified

Section: Genoma Viral E Proteínas Do Papilomavírusunclassified

Section: Ciclo Viralunclassified

Section: Introductionunclassified

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Potencial vacinal de proteínas recombinantes do capsídeo de papilomavírus humano.

Sakauchi¹

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Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against highrisk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd. INTRODUCTIONTargeting cancers for immunotherapy is often complicated by a lack of immunogenic tumour peptides. Mutated or overexpressed self-antigens are frequently the targets and invoke a generally low affinity/avidity T and B cell response. In contrast, the tight association between infection with HPV and cervical cancer means that foreign viral proteins encoded by HPV can provide the basis of either prophylactic or therapeutic cancer vaccines [1,2]. The natural course of anogenital HPV infection results in overwhelming clearance of the virus in 98% of individuals with an immune component suggested by the increased risk of HPV-associated cancers in immune-compromised organ transplant recipients [3,4]. However, HPV genotype-specific antibodies against the viral capsid proteins (L1 and L2) are produced at only low levels in about half the patients, can take close to a year to develop after natural infection and associate with higher viral loads in the cervix [5]. Thus, natural antibody may reflect the non-lytic, localised, intracellular nature of the infection leading to poor immunogenicity for immunoglobulin production and a greater emphasis on T-cell immunity for viral clearance. In contrast, prior immunization with HPV capsid proteins in animal studies induces high titres of antibody that are protective against challenge infection. Early studies in dogs demonstrated that prior immunization with L1 capsid protein could protect beagles from mucosal challenge with canine oral ...

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Genomic Applications in Head and Neck Cancers

Ahn

Agrawal

2014

Genomic Applications in Pathology

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Emerging human papillomavirus vaccines

Cited by 72 publications

References 157 publications

Potencial vacinal de proteínas recombinantes do capsídeo de papilomavírus humano.

Potencial vacinal de proteínas recombinantes do capsídeo de papilomavírus humano.

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

Genomic Applications in Head and Neck Cancers

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