Chitosan-based vaccine adjuvants: incomplete characterization complicates preclinical and clinical evaluation

Abstract

A number of preclinical and clinical studies with chitosan-adjuvanted antigen- and DNA-based vaccines have been carried out. Various chitosans and their modifications, in different forms (solutions, powders, gels and particles), have been evaluated with various antigens administered via different routes. Chitosan is a generic name for a wide array of glucosamine-based substances derived from biological sources, and standardization is necessary. However, in most of the studies published to date, molecular weight, viscosity, deacetylation degree and/or purity level (especially endotoxins) are not provided for the initial chitosan substance and/or final formulation and the preparation procedure is not detailed. Evaluation of adjuvant properties is challenging, given that the only available data are insufficient to demonstrate immunogenicity for chitosans with characteristics within certain intervals to elucidate mechanisms of action or to exclude impurities as the active substance. These and other issues of chitosan-based vaccine adjuvants are summarized and a step-by-step evaluation approach for chitosan-based vaccine adjuvants is outlined.

The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons

“…Proposed mechanisms underlying the adjuvanticity of chitosan include antigen protection, depot formation, enhanced antigen uptake and presentation and direct modulation of immune responses (Vasiliev, 2015). Another plausible suggestion is that chitosan-induced cell death might promote the release of DAMPs.…”

“…However, a major disadvantage of alum is its limited ability to efficiently drive T helper 1 (Th1) responses. The chitin derivative chitosan is an attractive alternative to alum, being biocompatible, flexible in terms of formulation and degree of deacetylation, and efficacious when administered mucosally (Vasiliev, 2015). We found that chitosan is superior to alum in promoting Th1 responses (Mori et al, 2012).…”

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

“…Key characteristics, such as chitosan’s molecular weight, degree of deacetylation, viscosity, and endotoxin levels [93], should be considered when testing chitosan for adjuvant applications. It would be helpful to refer Vasiliev’s (2015) step-by-step approaches in the proper evaluation and standardization of chitosan for use as vaccine-adjuvants [94]. …”

Polymeric Nanoparticles Engineered as a Vaccine Adjuvant-Delivery System

“…Chitosan, as a cationic polysaccharide bearing lots of reactive groups, possesses beneficial properties for vaccine formulation, including biocompatibility, flexibility in terms of formulation and degree of deacetylation, and efficacy when administered via mucosal route, and ability to promote immune responses [41,42], and thus is thought a superior alternative to alum which only favors promoting humoral responses [43]. Also, chitosan is thought suitable for constituting a mucosal VADS thanks to its bio-adhesive character and intrinsic adjuvanticity, which may arise from chitosan-mediated inflammasome activation [44], or from triggering certain type of PRRs such as TLR4 on immune cells [45], in consistence with its parent molecule chitin which is confirmed able to activate immunocytes via binding to mannose receptors and TLR2 to initiate innate immune responses [46].…”