Chitosan: a promising safe and immune-enhancing adjuvant for intranasal vaccines

Abstract

The nasal route is attractive for the delivery of vaccines in that it not only offers an easy to use, non-invasive, needle-free alternative to more conventional parenteral injection, but it also creates an opportunity to elicit both systemic and (crucially) mucosal immune responses which may increase the capability of controlling pathogens at the site of entry. Immune responses to "naked" antigens are often modest and it is widely accepted that incorporation of an adjuvant is a prerequisite for the achievement of clinically effective nasal vaccines. Many existing adjuvants are sub-optimal or unsuitable because of local toxicity or poor enhancement of immunogenicity. Chitosan, particularly chitosan salts, have now been used in several preclinical and clinical studies with good tolerability, excellent immune stimulation and positive clinical results across a number of infections. Particularly significant evidence supporting chitosan as an adjuvant for nasal vaccination comes from clinical investigations on a norovirus vaccine; this demonstrated the ability of chitosan (ChiSys®), when combined with monophosphoryl lipid, to evoke robust immunological responses and confer protective immunity following (enteral) norovirus challenge. This article summarizes the totality of the meaningful information (including key unpublished data) supporting the development of chitosan-adjuvanted vaccines.

Keywords: adjuvant; avian influenza; chitosan; diphtheria; intranasal; mucosa; norovirus; safety; vaccine.

Figure 1. Kaplan-Meier plot showing mortality (percent survival) of ferrets (n=6/group) following IT challenge with HPAI H5N1 virus (replotted from⁵⁵). Bold line = CSN and TM-CSN adjuvanted vaccines, dashed line = unadjuvanted vaccine (HA only), dotted line = placebo control. Abbreviations: CSN, chitosan glutamate; highly pathogenic avian influenza (HPAI), IT, intratracheal, TM-CSN, trimethylated chitosan.