Clearance of persistent HPV infection and cervical lesion by therapeutic DNA vaccine in CIN3 patients

• DOI: 10.1038/ncomms6317
• Publication Date: 2014-10-30T09:49:39Z
• Authors: Tae Jin Kim; Hyun-Tak Jin; Soo-Young Hur; Hyun Gul Yang; Yong Bok Seo; Sung Ran Hong; Chang-Woo Lee; Suhyeon Kim; Jung-Won Woo; Ki Seok Park; Youn-Young Hwang; Jaehan Park; In-Ho Lee; Kyung-Taek Lim; Ki-Heon Lee; Mi Seon Jeong; Charles D. Surh; You Suk Suh; Jong Sup Park; Young Chul Sung
• Keywords: Adult; 0301 basic medicine; FUSION PROTEIN; ANTIGEN; Uterine Cervical Neoplasms; CD8-Positive T-Lymphocytes; IMMUNOGENICITY; DENDRITIC CELLS; Article; Young Adult; 03 medical and health sciences; Vaccines, DNA; Humans; Papillomavirus Vaccines; E6; Immunity, Cellular; IMMUNE-RESPONSES; HUMAN-PAPILLOMAVIRUS; Papillomavirus Infections; NATURAL-HISTORY; Oncogene Proteins, Viral; Middle Aged; Uterine Cervical Dysplasia; 3. Good health; T-CELL DIFFERENTIATION; Antibody Formation; ELECTROPORATION; Female

Abstract Here, we demonstrate that electroporation-enhanced immunization with a rationally designed HPV DNA vaccine (GX-188E), preferentially targeting antigens to dendritic cells, elicits significant E6/E7-specific IFN-γ-producing T-cell response in all nine cervical intraepithelial neoplasia 3 (CIN3) patients. Importantly, eight out of patients exhibit an enhanced polyfunctional HPV-specific CD8 as shown by increase cytolytic activity, proliferative capacity and secretion effector molecules. Notably, seven display complete regression their lesions viral clearance within 36 weeks follow up. GX-188E administration does not elicit serious vaccine-associated adverse events at administered doses. These findings indicate the magnitude systemic is main contributing factor for histological, cytological virological responses, providing valuable insights into design therapeutic vaccines effectively treating persistent infections cancers humans.