Human papillomavirus type 16 and 18 E6 and E7 oncoproteins with lysosomal-associated membrane protein 1 trafficking domain (HPV-16/18 E6/E7-LAMP1)

The HPV-16/18 E6 and E7 oncoprotein antigens with a LAMP-1 trafficking domain is a therapeutic target construct used in DNA vaccines to treat HPV-associated diseases. The E6 and E7 proteins are the primary oncogenes of high-risk HPV types 16 and 18, acting by inhibiting the p53 and pRb tumor suppressor pathways, respectively (StatPearls, NBK448132). The inclusion of the Lysosomal-Associated Membrane Protein 1 (LAMP-1) trafficking domain is a strategic modification designed to enhance the immunogenicity of these viral proteins. By directing the expressed E6 and E7 antigens to the lysosomal compartment, the LAMP-1 domain facilitates their presentation on MHC class II molecules, which is critical for activating CD4+ T-helper cells (PMID: 15141015). This enhanced T-helper response subsequently bolsters the activation and expansion of CD8+ cytotoxic T-lymphocytes capable of identifying and destroying HPV-infected or malignant cells. This target is central to the development of immunotherapies like VGX-3100, which aim to provide a non-surgical treatment for cervical intraepithelial neoplasia (CIN) and other HPV-related dysplasias (PMID: 26387142). Overall, the construct serves as a blueprint for the immune system to recognize and eliminate cells expressing the drivers of HPV-induced carcinogenesis.

Other names

HPV16/18 E6/E7-LAMP1 fusionVGX-3100 antigensLAMP-1/E6/E7 fusion proteinHPV-16 E6/E7 and HPV-18 E6/E7 DNA vaccine antigens

The construct induces a T-cell mediated immune response where the LAMP-1 domain directs the E6 and E7 antigens to the MHC class II processing pathway, enhancing CD4+ T-cell help and CD8+ T-cell cytotoxicity against HPV-infected cells (PMID: 26387142, PMID: 15141015).