Induction of mucosal and systemic immune responses following oral immunization of mice with Lactococcus lactis expressing human papillomavirus type 16 L1

Human papillomavirus type 16 L1 (HPV16 L1) has shown considerable promise as a parenteral vaccine for prevention of cervical cancers. Here, we report the possibility of oral vaccination for HPV16 L1 using Lactococcus lactis (L. lactis) as a live vector. L. lactis MG1363 was transformed with two types of HPV16 L1-encoding plasmids for intracellular expression or secretion. L. lactis transformed with HPV16 L1-encoding plasmids retained biochemical lactic acid production capability. The mucosal and systemic immune responses were affected by the cellular location of expressed HPV16 L1 proteins in L. lactis. Serum IgG responses were induced after oral immunizations of L. lactis secreting HPV16 L1. Vaginal IgA immune responses were observed following oral immunization with L. lactis expressing HPV16 L1 in an intracellular form, but not with L. lactis secreting HPV16 L1. Furthermore, induction of HPV16 L1-specific mucosal immune responses was affected by immunization frequency. Six immunizations over 5 weeks were required to induce vaginal immune responses. The levels of HPV16 L1-specific vaginal IgA were maintained until 12 weeks after the first vaccination. These results suggest the feasibility of L. lactis as an oral vaccine vehicle of HPV16 L1 and demonstrate the importance of cellular loci of expressed antigen for induction of vaginal and systemic immune responses.