Next generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine.

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TitleNext generation polyphosphazene immunoadjuvant: Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine.
Publication TypeJournal Article
Year of Publication2021
AuthorsMarin, A, Chowdhury, A, Valencia, SM, Zacharia, A, Kirnbauer, R, Roden, RBS, Pinto, LA, Shoemaker, RH, Marshall, JD, Andrianov, AK
JournalNanomedicine
Volume33
Pagination102359
Date Published2021 Jan 18
ISSN1549-9642
Abstract

Poly[di(carboxylatomethylphenoxy)phosphazene] (PCMP), a new member of polyphosphazene immunoadjuvant family, is synthesized. In vitro assessment of a new macromolecule revealed hydrolytic degradation profile and immunostimulatory activity comparable to its clinical stage homologue PCPP; however, PCMP was characterized by a beneficial reduced sensitivity to the ionic environment. In vivo evaluation of PCMP potency was conducted with human papillomavirus (HPV) virus-like particles (VLPs) based RG1-VLPs vaccine. In contrast with previously reported self-assembly of polyphosphazene adjuvants with proteins, which typically results in the formation of complexes with multimeric display of antigens, PCMP surface modified VLPs in a composition dependent pattern, which at a high polymer-to VLPs ratio led to stabilization of antigenic particles. Immunization experiments in mice demonstrated that PCMP adjuvanted RG1-VLPs vaccine induced potent humoral immune responses, in particular, on the level of highly desirable protective cross-neutralizing antibodies, and outperformed PCPP and Alhydrogel adjuvanted formulations.

DOI10.1016/j.nano.2021.102359
Alternate JournalNanomedicine
PubMed ID33476764
Grant ListR01 AI132213 / AI / NIAID NIH HHS / United States