Project 1

Less than 85% of cervical cancers occur in developing country populations that are hard to reach with a vaccine like Gardasil9 requiring a cold chain. Since they currently lack access to either cervical screening or HPV vaccination, our overall goal is to develop an affordable HPV vaccine that both extends the breadth of protection to all oncogenic types (to include those not covered by Gardasil9 and found preferentially in African American and Hispanic populations in the US), and is stable at ambient temperature. This is an important opportunity to reduce the global burden of cervical cancer, regardless of race, income or location. We generated a monoclonal antibody (mAb) RG1 reactive against the HPV16 L2 protein and able to cross-neutralize several key oncogenic HPV types. The HPV16L2 RG1 epitope was cloned into the DE surface loop of HPV16 L1.

Based on previous data produced by investigators in the Cervical Cancer SPORE, we have successfully obtained a patent in several countries, a commercial licensee (Pathovax LLC) and an NCI PREVENT award for our novel RG1-VLP based vaccine. The PREVENT program is producing GMP grade RG1-VLPs at Paragon Inc., Baltimore, MD, for our use, and will fund a preclinical toxicology study in support of the IND. We have already held a pre-IND meeting and received FDA input on the proposed pre-clinical and clinical study designs. Pathovax LLC has initiated a head-to-head comparison with Gardasil9, and shown that vaccination of rabbits with RG1-VLPs adjuvanted with aluminum hydroxide (alum) provides robust protection against experimental challenge with all HPV types tested to date.

Aim 1: Develop a GLP freeze-dry protocol for a powder formulation of RG1-VLPs in alum and study its in vitro temperature stability, and in murine models test its immunogenicity and protective efficacy in comparison to Gardasil9.

Aim 2: To perform a Dose Escalation Phase I Trial of the Safety and Immunogenicity of RG1-VLP in 36 healthy female volunteers with the inclusion of a control Gardasil9 arm in the study.

Aim 3: To analyze the levels of protective antibodies in the serum of patients from the phase I study induced by RG1-VLP vaccination or Gardasil9. We will utilize the passive transfer assay to measure protective responses, as well as L2 and L1 VLP ELISA and in vitro neutralization assays to quantify antigen-specific neutralizing antibody titers in serum.

Investigators

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