Nanocellulose as Novel Vaccine Adjuvant: Innate Immune Activation and Biocompatibility

Abstract

Aluminum remains the most widely accepted adjuvant to enhance the immunogenicity of vaccines. However, the clinical use of Aluminum is limited by its neurotoxicity and risk of immunoglobulin E production. Thus, alternative adjuvants with equivalent capability but higher biocompatibility are urgently needed. Among them, nanocellulose is a promising candidate for this purpose. In spite of their biodegradability, their physicochemical properties, including fibrillar nature, crystalline phase, and surface reactivity, affect their activation kinetics, and the relationship remains mostly unknown. Hence, I established a small library of nanocellulose materials using acid hydrolysis to obtain three CNCs with different sizes, aiming to investigate how the size of nanocellulose influences their biocompatibility and immunogenicity. I evaluated their proinflammatory effect on THP-1 cells, a monocyte cell line isolated from the peripheral blood of an acute monocytic leukemia patient, and J774, a murine macrophage cell. Then, I tested their cytotoxicity to both cells and compared their differential effects in IL-1β production. Finally, I correlated their proinflammatory adjuvant effects with their length. In conclusion, I found the production of IL-1β is CNC length-dependent but in a nonlinear relationship. By testing cell viability after stimulation with adjuvants, I found CNCs are a more biocompatible adjuvant than Alum, and the cytotoxicity of CNCs is also size-dependent. This study provides a preliminary demonstration of the optimal length range and crystallinity of CNCs that could induce the most adjuvant effects without posing cytotoxicity.