Current human papillomavirus (HPV) vaccines provide substantial protection against several common HPV types, but many circulating cancer-causing types remain for which vaccine coverage is lacking.  In addition, all current HPV vaccines rely on aluminum salt-based adjuvant formulations that function through unclear mechanisms with few substitutes available.  In an effort to expand the toolbox of available adjuvants suitable for HPV vaccines, we compared the immunogenicity of the RG1-VLP (virus-like particle) vaccine in BALB/c mice when formulated with either the aluminum hydroxide adjuvant Alhydrogel or the novel polyphosphazene macromolecular adjuvant poly[di(carboxylatoethylphenoxy)phosphazene] (PCEP).  PCEP-formulated RG1-VLPs routinely outperformed VLP/Alhydrogel in several measurements of VLP-specific humoral immunity, including consistent improvements in the magnitude of antibody responses to both HPV16-L1 and the L2 RG1 epitope as well as cross-neutralizing titers to HPV18 and HPV39.  Dose-sparing studies indicated that RG1-VLPs could be reduced in dose by 75% in the presence of PCEP, while achieving activity comparable to a full VLP dose adjuvanted by Alhydrogel.  In addition, levels of HPV-binding and -neutralizing Abs were induced after two vaccinations with PCEP as adjuvant that were equivalent to or greater than levels achieved with 3 vaccinations with Alhydrogel alone.  A diversity in immune profiles was found to result from the formulation of VLPs with polyphosphazenes, suggesting disparate mechanisms.  These data suggest that substitution of aluminum salts with PCEP for VLP-based HPV vaccines could lead to rapid seropositivity requiring fewer boosts, dose-sparing, and the establishment of longer-lasting memory responses to HPV.

Improved novel HPV vaccine performance by substitution of alum with polyphosphazene adjuvant PCEP

ACS Spring 2022

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