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

Abstract

Adjuvants are central to the efficacy of subunit vaccines. Although several new adjuvants have been approved in human vaccines over the last decade, the panel of adjuvants in licensed human vaccines remains small. There is still a need for novel adjuvants that can be safely used in humans, easy to source and to formulate with a wide range of antigens and would be broadly applicable to a wide range of vaccines. In this article, using the Respiratory Syncytial Virus (RSV) nanoparticulate prefusion F model antigen developed by Sanofi, we demonstrate in the macaque model that the polyacrylate (PAA)-based adjuvant SPA09 is well tolerated and increases vaccine antigen-specific humoral immunity (sustained neutralizing antibodies, memory B cells and mucosal immunity) and elicits strong T H 1-type responses (based on IFNγ and IL-2 ELISpots) in a dose-dependent manner. These data warrant further development of the SPA09 adjuvant for evaluation in clinical trial.

Adjuvants: Engineering Protective Immune Responses in Human and Veterinary Vaccines

“…SPA09 has been shown to induce robust Th1-biased cellular and humoral responses in combination with various antigens, particularly the recombinant cytomegalovirus glycoprotein B (CMV-gB) and a Staphylococcus aureus polysaccharide conjugate in mice [274]. A similar effect was recently observed in cynomolgus macaques upon immunization with SPA09 in combination with respiratory syncytial virus (RSV) nanoparticulate prefusion F model antigen [273].…”

“…Currently, the adenovirus-based cocaine vaccine dAd5GNE co-delivered with the Adjuplex™ (Advanced BioAdjuvants LLC) platform, which is based on purified lecithin and carbomer homopolymer, is being evaluated in a Phase I clinical study [269][270][271][272]. SPA09, a novel vaccine adjuvant based on high molecular weight straight PAA, is also being developed by Sanofi Pasteur for evaluation in clinical trials [263,273,274]. It provides the key advantages of ease of synthesis and quality control, as well as cost-effectiveness over other PAA-based formulations due to its simple structure and the commercial availability of straight PAAs [263].…”

Oral immunocontraceptive vaccines: A novel approach for fertility control in wildlife

“…Both linear and branched PMA have been used in oral vaccine delivery systems as it can protect peptide antigens from enzymatic degradation, induce strong humoral and cellular immune response. 80,81 PMA-group A Streptococcus M protein antigen conjugate has been applied against group A Streptococcus. 82 Recently, a contraceptive vaccine consisting of GnRH, universal T helper epitope PADRE (P) and PMA self-assembled into nanoparticles and produced high titers of IgG after oral and subcutaneous immunization in mice, which was more effective than cholera toxin B adjuvanted positive control.…”

“…Further studies are needed to investigate the ability of oral DNA vaccine to stimulate mucosal or systemic immunity. Both linear and branched PMA have been used in oral vaccine delivery systems as it can protect peptide antigens from enzymatic degradation, induce strong humoral and cellular immune response 80,81 . PMA‐group A Streptococcus M protein antigen conjugate has been applied against group A Streptococcus 82 .…”

Characterization of antigen adjuvant interactions in polyacrylate adjuvanted vaccines

“…This linear (i.e. non-crosslinked) polyacrylate demonstrated good safety, tolerability and strong adjuvant effects in mice and non-human primates [ 9 , 10 ]. Owing to its potential advantages in terms of manufacturability, stability, and potency, SPA09 has recently entered human clinical testing.…”