There are over 200 related subtypes of human papillomavirus (HPV), of which 15 have been identified that can cause cancer including cervical, anogenital, and oropharyngeal cancers. Although only a small percentage of HPV types are oncogenic, it is estimated that these oncogenic HPV types cause approximately 5% of all cancers worldwide. Current HPV vaccines use L1 capsid protein virus-like particles (VLPs) as antigens for generating type-specific neutralizing antibodies. However, the type-specific efficacies of these vaccines limit their breadth (only protecting against, at most, 8 different HPV types), thus highlighting the need for more broadly protective vaccines.
Researchers at the Biodesign Institute of Arizona State University have developed two novel HPV minor capsid protein L2-based broadly protective mucosal vaccine candidates. The first of these two vaccine candidates utilizes L2 displayed on the surface of hepatitis B core (HBc) virus-like particles and the second utilizes L2 genetically fused to an immunoglobulin capable of forming recombinant immune complexes (RICs). Both candidates were immunogenic on their own, in mice, but were especially so when delivered together. A plant expression system was used for high scalability, low upstream costs and to create a product with minimal human/animal pathogen contaminants.
These L2-based VPL and RIC platforms demonstrate the potential for a combined, highly effective, synergistic vaccine delivery system for more safe and affordable HPV vaccination.
• HPV vaccines
o VLP based vaccine
o RIC based vaccine
o Co-delivered VLP and RIC based vaccine
Benefits and Advantages
• Amenable to mucosal delivery
• L2 antibodies can provide protection against multiple HPV types
• Enhanced stability and immunogenicity
o Specific VLP arrangement allows formation of HBc dimers with only a single copy of L2 for increased stability
o Consistently elicits very high titers (>1,000,000) of L2 antibody which neutralized HPV infectivity
• Broad coverage for HPV types
• Plant expression system - high scalability, lack of human/animal pathogens and low upstream costs
o Produces high levels of recombinant protein, up to 30-50% of the total soluble plant protein in 4-5 days
o Milligram quantities of fully assembled HBc VLPs displaying HPV L2 can be produced and purified through a simple one-step purification process
o More homogeneous glycoforms for improved interaction with Fc gamma and complement receptors
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