Optimizing adjuvants for intradermal delivery of MenC glycoconjugate vaccine

Abstract

Intradermal vaccine delivery is a promising alternative to the conventional intramuscular route. The skin layer is immunologically supported by a densely network of antigen presenting cells, while the skeletal muscle is loaded with a relatively sparse population of APCs. Nevertheless, the vaccine to be suitable for intradermal delivery needs a new formulation to facilitate either smaller injection volumes or the introduction into new delivery devises as micro-needles. This study presents a proof of concept for intradermal delivery of the MenC-CRM197 glycoconjugate vaccine using a mouse model. Tangential flow filtration allowed obtaining a 20-fold concentrated vaccine formulation suitable for intradermal injection. Importantly the intradermal delivery of non-adjuvanted MenC glycoconjugate vaccine showed a quicker on-set and superiority in terms of immunogenicity compared to intramuscular administration of the respective vaccine and comparable immunogenicity to the aluminum adjuvanted vaccine formulation given intramuscular. Subsequently, the use of adjuvants allowed to further increase the immunogenicity and to modulate the quality of the immune response towards a more beneficial Th1 response. As adjuvants two Toll like receptor agonists (TLR4a and TLR7a), a mutant of the heat-labile enterotoxin from Escherichia coli (LT), a α-GalactosylCeramide analogue and an oil in water emulsion were investigated in order to target skin-resident antigen-presenting cells. This approach has the potential to be extended to other meningococcal serogroups, representing a promising strategy for the development of dermally administered multivalent glycoconjugate vaccines.