A potent novel vaccine adjuvant based on straight polyacrylate

被引:6
作者
Garinot, Marie [1 ]
Piras-Douce, Fabienne [1 ]
Probeck, Patricia [2 ]
Chambon, Veronique [3 ]
Varghese, Kucku [4 ]
Liu, Yuanqing [1 ]
Luna, Ernesto [5 ]
Drake, Donald [5 ]
Haensler, Jean [1 ]
机构
[1] Sanofi Pasteur, Res & External Innovat, Marcy Letoile, France
[2] Sanofi Pasteur, Clin Supply Chain, Marcy Letoile, France
[3] Sanofi Pasteur, Analyt Sci, Marcy Letoile, France
[4] Sanofi Pasteur, Global Clin Immunol, Swiftwater, PA USA
[5] Sanofi Pasteur, Orlando, FL USA
关键词
Polyacrylate; SPA09; Adjuvant; Vaccine; Cytomegalovirus (CMV); ADAPTIVE IMMUNE-RESPONSES; POLY(ACRYLIC ACID); ANTIBODY-RESPONSES; CARBOMER; DELIVERY; SAFETY; POLYELECTROLYTES; FORMULATION; PREVENTION; COMPLEXES;
D O I
10.1016/j.ijpx.2020.100054
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
A structure-activity study was conducted to identify the structural characteristics underlying the adjuvant activity of straight (i.e. non-crosslinked) polyacrylate polymers (PAAs) in order to select a new PAA adjuvant candidate for future clinical development. The study revealed that the adjuvant effect of PAA was mainly influenced by polymer size (Mw) and dose. Maximal effects were obtained with large PAAs above 350 kDa and doses above 100 mu g in mice. Small PAAs below 10 kDa had virtually no adjuvant effect. HPSEC analysis revealed that PAA polydispersity index and ramification had less impact on adjuvanticity. Heat stability studies indicated that residual persulfate could be detrimental to PAA stability. Hence, this impurity was systematically eliminated by diafiltration along with small Mw PAAs and residual acrylic acid that could potentially affect product safety, potency and stability. The selected PAA, termed SPA09, displayed an adjuvant effect that was superior to that of a standard emulsion adjuvant when tested with CMV-gB in mice, even in the absence of binding to the antigen. The induced immune response was dominated by strong IFN gamma, IgG2c and virus neutralizing titers. The activity of SPA09 was then confirmed on human cells via the innate immune module of the human MIMIC (R) system.
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页数:11
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