TY - JOUR
T1 - Next generation polyphosphazene immunoadjuvant
T2 - Synthesis, self-assembly and in vivo potency with human papillomavirus VLPs-based vaccine
AU - Marin, Alexander
AU - Chowdhury, Ananda
AU - Valencia, Sarah M.
AU - Zacharia, Athina
AU - Kirnbauer, Reinhard
AU - Roden, Richard B.S.
AU - Pinto, Ligia A.
AU - Shoemaker, Robert H.
AU - Marshall, Jason D.
AU - Andrianov, Alexander K.
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - Immunostimulating compounds
KW - Polyphosphazenes
KW - Self-assembly
KW - Vaccine delivery
KW - Virus-like particles
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UR - http://www.scopus.com/inward/citedby.url?scp=85100419594&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2021.102359
DO - 10.1016/j.nano.2021.102359
M3 - Article
C2 - 33476764
AN - SCOPUS:85100419594
SN - 1549-9634
VL - 33
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
M1 - 102359
ER -