PCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection

PCPP, a well-defined polyphosphazene macromolecule, has been studied as an immunoadjuvant for a soluble form of the postfusion glycoprotein of respiratory syncytial virus (RSV sF), Which is an attractive vaccine candid-ate for inducing RSV-specific immunity in mice and humans. We demonstrate that RSV sF-PCPP formulations induce high neutralization titers to RSV Comparable to alum formulations even at a low PCPP dose and protect animals against viral challenge both in the lung and in the upper respiratory tract. PCPP formulations were also characterized by Th1-biased responses, compared to Th2-biased responses that are more typical for RSV sF alone or RSV sF alum formulations, suggesting an inherent immunostimulating activity of the polyphosphatene adjuvant. We defined these immunologically active RSV sF- PCPP formulations as self-asSembled water-Soluble protein-polymer complexes with distinct physicochemical-parameters The secondary structure and antigenicity of the protein in the complex were fully preserved during the spontaneous aqueous self assembly process. These findings further advance the concept cif polyphosphazene immunoadjuvants as unique dual-functionality adjuvants integrating delivery and immunostimulating modalities in one water-soluble molecule.

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