Victoria Juarez, H Amalia Pasolli, Andrea Hellwig, Natalio Garbi, Angel Cid Arregui
{"title":"Virus-Like Particles Harboring CCL19, IL-2 and HPV16 E7 Elicit Protective T Cell Responses in HLA-A2 Transgenic Mice.","authors":"Victoria Juarez, H Amalia Pasolli, Andrea Hellwig, Natalio Garbi, Angel Cid Arregui","doi":"10.2174/1874357901206010270","DOIUrl":null,"url":null,"abstract":"<p><p>Infection by high-risk genotypes of human papillomaviruses (HR-HPVs) is the cause of cancer of the uterine cervix. Although prophylactic vaccines directed against the two most prevalent HR-HPV types (HPV16 and 18) have been commercialized recently, there is a need for effective therapeutic vaccines against HR-HPVs. We have tested in mice a chimeric protein composed of the hepatitis B small surface antigen (HBsAg(S)) flanked at its N-terminus by chemokine CC ligand 19/macrophage inflammatory protein-3β (CCL19/MIP-3β), and at the C-terminus by interleukin 2 (IL-2) and an artificial HPV16 E7 polytope. This protein is assembled into nanoparticles and both CCL19 and IL-2 conserve their functionality. HLA-A2 (AAD) transgenic mice immunized with a plasmid encoding this protein mounted specific T cell responses against E7 without the need of an adjuvant. Furthermore, vaccination prevented the development of tumors after implantation of the E6/E7-expressing TC-1/A2 tumor cell line. Our results suggest that vaccines based on HBsAg(S) nanoparticles carrying short E7 epitopes and immune-stimulatory domains might be of therapeutic value in the treatment of patients suffering from cervical pre-cancer or cancer lesions caused by HR-HPVs.</p>","PeriodicalId":23111,"journal":{"name":"The Open Virology Journal","volume":"6 ","pages":"270-6"},"PeriodicalIF":0.0000,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1874357901206010270","citationCount":"20","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Open Virology Journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1874357901206010270","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2012/12/28 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 20
Abstract
Infection by high-risk genotypes of human papillomaviruses (HR-HPVs) is the cause of cancer of the uterine cervix. Although prophylactic vaccines directed against the two most prevalent HR-HPV types (HPV16 and 18) have been commercialized recently, there is a need for effective therapeutic vaccines against HR-HPVs. We have tested in mice a chimeric protein composed of the hepatitis B small surface antigen (HBsAg(S)) flanked at its N-terminus by chemokine CC ligand 19/macrophage inflammatory protein-3β (CCL19/MIP-3β), and at the C-terminus by interleukin 2 (IL-2) and an artificial HPV16 E7 polytope. This protein is assembled into nanoparticles and both CCL19 and IL-2 conserve their functionality. HLA-A2 (AAD) transgenic mice immunized with a plasmid encoding this protein mounted specific T cell responses against E7 without the need of an adjuvant. Furthermore, vaccination prevented the development of tumors after implantation of the E6/E7-expressing TC-1/A2 tumor cell line. Our results suggest that vaccines based on HBsAg(S) nanoparticles carrying short E7 epitopes and immune-stimulatory domains might be of therapeutic value in the treatment of patients suffering from cervical pre-cancer or cancer lesions caused by HR-HPVs.