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

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TitlePCPP-Adjuvanted Respiratory Syncytial Virus (RSV) sF Subunit Vaccine: Self-Assembled Supramolecular Complexes Enable Enhanced Immunogenicity and Protection.
Publication TypeJournal Article
Year of Publication2017
AuthorsCayatte, C, Marin, A, Rajani, GManohar, Schneider-Ohrum, K, Bennett, ASnell, Marshall, JD, Andrianov, AK
JournalMol Pharm
Date Published2017 Jun 07
ISSN1543-8392
Abstract

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 candidate 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 polyphosphazene 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 of polyphosphazene immunoadjuvants as unique dual-functionality adjuvants integrating delivery and immunostimulating modalities in one water-soluble molecule.

DOI10.1021/acs.molpharmaceut.7b00118
Alternate JournalMol. Pharm.
PubMed ID28544850