Prophylactic immunization with human papillomavirus vaccines induces oral immunity in mice

Abstract

Objective: Although it has been shown that prophylactic vaccination can induce genital immunity, there is inadequate information on human papillomavirus (HPV) vaccine-induced oral immunity, which is of particular interest due to HPVassociated oropharyngeal malignancies and recurrent respiratory papillomatosis. Therefore, we assessed the efficacy of various HPV vaccines against oral HPV pseudovirus (PsV) infection in mice.Study Design: Preclinical scientific investigation.Methods: C57BL/6 mice were vaccinated three times at 2-week intervals with either Gardasil (Merck, Kenilworth, NJ) (50 mL intramuscular injection) or a candidate pan-HPV L2 vaccine with alum adjuvant (25 mg subcutaneous injection). Additional mice were immunized with passive transfer of either Gardasil (Merck) human antisera or nonimmunized sera (100 mL intraperitoneal injection). All vaccinated and na€ ıve control mice were then challenged with HPV16 E6E7 luciferase PsV in the oral mucosa. Visualization of HPV PsV infection was monitored through in vivo luciferase imaging.Results: Oral luciferase-expressing HPV16 PsV infection was not detected in Gardasil (Merck), L2 vaccine, and Gardasil (Merck) antisera-immunized mice, whereas robust luciferase expression was observed in all control mice. An in vitro neutralization assay from sera of Gardasil-vaccinated (Merck) mice confirmed that vaccine efficacy was due to neutralizing antibodies.Conclusion: Oral HPV16 PsV infection in mice was completely prevented with all methods of prophylactic HPV immunization. These findings provide preliminary evidence that human vaccines induce protection against oral HPV infection, which has significant public health implications for HPV-associated oropharyngeal malignancies.

A Current Update on Human Papillomavirus-Associated Head and Neck Cancers

“…Preclinical studies have gone further to assess, in mice, the potential of Gardasil-4 and other candidate HPV vaccines (under development) to protect against oral HPV infections. In one study, it was demonstrated that mice intramuscularly immunized with Gardasil-4 or with a pan-HPV L2 vaccine (a candidate HPV vaccine targeting broadly neutralizing epitopes on the minor capsid) were protected from oral infection with HPV pseudovirus 16 [78]. Recently, we showed that mice orally immunized with mixed MS2-L2 VLPs (a bacteriophage-based candidate HPV vaccine composed of MS2-16L2/31L2 and MS2-Cons69-86) were protected from infection following oral infection with HPV pseudoviruses 16, 35, 39, 52, and 58 [79]; these HPV types are associated with ~80% of HPV + HNC cases.…”

Oral immunization with bacteriophage MS2-L2 VLPs protects against oral and genital infection with multiple HPV types associated with head & neck cancers and cervical cancer

“…Two prophylactic vaccines (Gardasil-9 and Cervarix; Gardasil-4 is discontinued) are currently approved to protect against HPV infection. Gardasil-4, which protected against HPV6, HPV11, HPV16 and HPV18 has been shown to elicit oral IgG antibodies [33,34], oral antibodies neutralize/protect against HPV6, HPV16, HPV18 [35,36], and reduce oral prevalence of vaccine types (HPV types included in the vaccine) in vaccinees [37][38][39]. However, a protective effect of the vaccine on HPV types not included in the vaccine was not observed.…”

Implementation of Routine HPV Vaccination in the Management of Recurrent Respiratory Papillomatosis

“…The international FUTURE I/II trials showed that quadrivalent HPV vaccination provided sustained protection of 96% to 100% against anogenital condylomas and low-grade cervical and vulvovaginal neoplasias caused by HPV types 6, 11, 16, and 18. 19 Complementing the established research on genital immunity, Ahn et al 20 were the first to show that the vaccine was also effective in inducing oral immunity against HPV16 in a murine model.…”