A potent novel vaccine adjuvant based on straight polyacrylate

Abstract

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 μg 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 IFNγ, IgG2c and virus neutralizing titers. The activity of SPA09 was then confirmed on human cells via the innate immune module of the human MIMIC® system.

A novel vaccine adjuvant based on straight polyacrylate potentiates vaccine-induced humoral and cellular immunity in cynomolgus macaques

“…38 Regarding the mechanism of action, our previous studies using SPA09 with the CMV-gB antigen suggested that SPA09 could exert adjuvant activity without apparent interaction with the vaccine antigen. 8 This feature remains to be assessed for the Pre-F-NP and other antigens. Indeed, the polyelectrolyte adjuvants are generally described as dual-functionality adjuvants integrating immunostimulatory and delivery modalities, the latter depending strongly on the ability of the antigen to interact with the adjuvant.…”

“…[5][6][7] We recently introduced a novel adjuvant, termed SPA09, based on high molecular weight linear polyacrylate readily available and easy to formulate with vaccine antigens. 8 In previous studies in mice, SPA09 was found to work as a strong T H 1-type adjuvant when tested with various types of antigens including the recombinant glycoprotein CMV-gB and a Staphylococcus aureus polysaccharide conjugate (patent WO2017218819A1). It was found to be more potent than MF59 (squalene oil-in-water emulsion -Novartis) when tested with CMV-gB.…”

“…SPA09 was also capable of activating human antigen-presenting cells in vitro when tested via the innate immune module of the human MIMIC® system (patent WO2017218819A1). 8 Although mouse models are useful to the evaluation of adjuvant effect and mechanism, they are not fully predictive of innate and adaptive immunity after vaccination in humans. Non-human primates (NHPs) are considered to be more translatable models of human vaccine responses due to the high degree of similarity in the distribution and function of immune cell subsets.…”

A TLR7/8 Agonist-Including DOEPC-Based Cationic Liposome Formulation Mediates Its Adjuvanticity Through the Sustained Recruitment of Highly Activated Monocytes in a Type I IFN-Independent but NF-κB-Dependent Manner

“…or intraperitoneally (i.p. ), with 2 μg of gB-CMV [SANOFI Pasteur, prepared as described in ( 34 )], adjuvanted with cationic liposomal formulations (SANOFI Pasteur) including 100 μg 1,2-dioleoyl- sn -glycero-3-ethylphosphocholine (chloride salt) (DOEPC; Avanti Polar Lipids, Alabaster, AL, USA) without (SPA06) or with (SPA10) 17.5 μg 3M-052, in a final volume of 50 μl. These doses were each experimentally defined as optimal in preliminary dose optimization studies.…”

“…In this study, we used the glycoprotein B (gB) of cytomegalovirus ( 34 ) as a model antigen to investigate the mechanisms by which a DOEPC-based cationic liposome formulation including the 3M-052 TLR 7/8 agonist (hereafter named SPA10) exerts its adjuvanticity in comparison to the plain DOEPC-based cationic liposome formulation (hereafter named SPA06), used as control. We show that strong and sustained germinal center (GC) B cell and T follicular helper (T FH ) cell responses are induced by SPA10, associated with a prolonged recruitment/homing of highly activated antigen-loaded monocytes and monocyte-derived dendritic cells (Mo-DCs) toward the injection site and draining lymph nodes (dLNs), and that SPA10-mediated B cell adjuvanticity is type I interferon-independent but NF-κB-dependent.…”