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Abstract
Diverse HPV subtypes are responsible for considerable disease burden worldwide, necessitating
safe, cheap, and effective vaccines. The HPV minor capsid protein L2 is a promising
candidate to create broadly protective HPV vaccines, though it is poorly immunogenic
by itself. To create highly immunogenic and safe vaccine candidates targeting L2,
we employed a plant-based recombinant protein expression system to produce two different
vaccine candidates: L2 displayed on the surface of hepatitis B core (HBc) virus-like
particles (VLPs) or L2 genetically fused to an immunoglobulin capable of forming recombinant
immune complexes (RIC). Both vaccine candidates were potently immunogenic in mice,
but were especially so when delivered together, generating very consistent and high
antibody titers directed against HPV L2 (>1,000,000) that correlated with virus neutralization.
These data indicate a novel immune response synergy upon co-delivery of VLP and RIC
platforms, a strategy that can be adapted generally for many different antigens.