Testing RG1-VLP Vaccine to Prevent HPV-related Cancers

PRIMARY OBJECTIVE: I. Assess the safety of RG1-virus-like particles (VLP) in healthy 18-60 years old women at 3 escalating doses. SECONDARY OBJECTIVES: I. Determine the immunogenicity of RG1-VLP in healthy 18-60 year old women at 3 escalating doses via the following assays: Ia. Determine serum antibody responses induced by RG1-VLP vaccination by both human papillomavirus (HPV) 16 L1 VLP and HPV16 L2 RG1-peptide enzyme-linked immunosorbent assay (ELISA). This will be assessed at months 0, 1, 2, 3, 6, 7 and 12; Ib. Determine whether vaccination-induced serum antibody response neutralizes HPV16. This will be assessed at months 0, 1, 2, 3, 6, 7 and 12. EXPLORATORY OBJECTIVES: I. Determine whether vaccination-induced serum antibody response broadly neutralizes high risk (hr) HPV other than HPV16. This will be assessed at months 0, 1, 2, 3, 6, 7 and 12. II. Determine whether vaccination induces a cell-mediated immune (CMI) response. Peripheral blood mononuclear cells (PBMC) will be isolated at months 0, 1 and 7. III. Determine whether vaccination-induced serum antibody response upon passive transfer to naive animals, protects mice against hrHPV pseudovirion (PsV) challenge. This will be assessed at months 0 and 7. IV. Determine whether vaccination results in changes in local antibody titers in vaginal and oral secretions (via oral rinse) and the effects of vaccination on HPV types in optionally-collected vaginal and oral secretions and eyebrow hair samples between months 0, 7 and 12. V. Assess the safety of recombinant human papillomavirus nonavalent vaccine (Gardasil-9) in healthy women post-administration of RG1-VLP. OUTLINE: This is a dose-escalation study of RG1-VLP. Patients receive RG1-VLP intramuscularly (IM) for 3 doses at months 0, 2, and 6 in the absence of unacceptable toxicity. Patients may also receive Gardasil-9 via injection for 3 doses at 6 months after the 3rd study vaccination (month 12), then at months 14 and 18 in the absence of unacceptable toxicity. Patients also undergo blood sample collection on study and may undergo vaginal swab collection on study. After completion of study treatment, patients are followed up to 6 months post-3rd RG1-VLP vaccination injection or up to 14 days post-3rd Gardasil-9 vaccination.