HPV?=?human papillomavirus. Discussion We found that vaccination with the multimeric fusion proteins comprising the amino terminus of L2 of several HPV types induced robust neutralizing antibody titers, and when used with potent adjuvants, it also provided immunity from viral challenge even 4 months after immunization. 3 (HPV types 6, 16, 18), 11-88 5 (HPV types 1, 5, 6, 16, 18), or 17-36 22 (five cutaneous, two mucosal low-risk, and 15 oncogenic types), that were formulated alone or in GPI-0100, alum, or 1018 ISS adjuvants were compared with vaccination with Gosogliptin L1 virus-like particles (VLPs), including Gardasil, a licensed quadrivalent HPV L1 vaccine, and a negative control. Mice were challenged with HPV-16 pseudovirions 4 months after vaccination. Statistical tests were two-sided. Results The HPV-16 L2 polypeptides generated robust HPV-16Cneutralizing antibody responses, albeit lower than those to HPV-16 L1 VLPs, and lower responses against other HPVs. In contrast, vaccination with the multitype L2 fusion proteins 11-200 x 3 and 11-88 x 5 induced high serum neutralizing antibody titers against all heterologous HPVs tested. 11-200 3 formulated in GPI-0100 adjuvant or alum with 1018 ISS protected mice against HPV-16 challenge (reduction in HPV-16 infection vs phosphate-buffered saline control, < .001) 4 months after vaccination as well as HPV-16 L1 VLPs, but 11-200 3 alone or formulated with either alum or 1018 ISS was less effective (reduction in HPV-16 infection, < .001). Conclusion Concatenated multitype L2 proteins in adjuvant have potential as pan-oncogenic HPV vaccines. CONTEXT AND CAVEATS Prior knowledgeCurrent human papillomavirus (HPV) vaccines are based on capsid L1 proteins and appear to confer only HPV typeCspecific immunity. Although vaccination with minor capsid protein L2 induces antibodies that neutralize many types of papillomaviruses, the response Gosogliptin to the specific virus type is usually higher than it is to other types. Study designMice were vaccinated with HPV-16 L2 polypeptides, multitype L2 fusion proteins in different adjuvants, Gardasil, HPV-16 L1 virus-like particles (VLPs), or a negative control, followed by challenge with HPV-16 pseudovirions 4 months later. ContributionsVaccination with the multitype L2 fusion proteins induced antibody responses to all HPV types tested and protected mice against HPV-16 challenge as well as HPV-16 L1 VLPs. ImplicationsMultitype L2 proteins have potential as pan-oncogenic HPV vaccines. LimitationsTo be effective in humans, the vaccine will need to protect against infection for several years; only short times were tested in this study. From the Editors The discovery that persistent infection with oncogenic human papillomavirus (HPV) types, of which 15 have been identified (1), is a necessary cause of cervical cancer has driven the development of prophylactic vaccines that are based on the capsid proteins L1 and L2 (2). Vaccination with L1 virus-like particles (VLPs) (3C5) elicits high, but type-restricted, titers of neutralizing antibodies, which appear to be the main mediators of protection (3,6C9). VLP vaccines confer a high degree of protection against infection and neoplastic disease caused by the papillomavirus types used to derive the vaccine (10C12). Current formulations of the two licensed L1 VLP vaccines (Gardasil, Merck & Co., Inc., and Cervarix, GlaxoSmithKline) contain two oncogenic HPV genotypes, HPV-16 and HPV-18, which together account for about 70% of cervical cancers (11,13). Gardasil also contains L1 VLP types that are derived from HPV-6 and HPV-11 and prevents benign genital warts caused by these viruses. If protection induced by L1 VLP vaccines is predominantly HPV type specific, it would be necessary to incorporate VLPs from nine oncogenic HPV types to prevent greater than 90% of cervical cancers (14). Although L1 Rabbit Polyclonal to OR9Q1 VLP vaccination may induce partial cross-protection against very closely related HPV types (12,15), which is likely mediated by relatively low levels of cross-type neutralizing antibodies (8,16), comprehensive vaccination against all oncogenic HPV types is challenging because of the cost and complexity of developing highly multivalent L1 VLP vaccines (17). The possibility of a single protein, inexpensive, pan-oncogenic HPV vaccine is an attractive Gosogliptin alternative to highly Gosogliptin multivalent and thus costly L1 VLP.