Alpha-D-glucan-based vaccine adjuvants: Current status and future perspectives

Abstract

Nanoparticles (NPs) are increasingly used as efficient vaccine antigen-delivery platforms and vaccine adjuvants. Alpha (α)-D-glucans are polysaccharide polymers found in plants, animals, and microbes. Phytoglycogen (PG) is a densely branched dendrimer-like α-D-glucan that forms nanoparticle structures. Two simple chemical modifications of corn-derived PG create positively charged, amphiphilic nanoparticles, known as Nano-11, that stimulate immune responses when used as vaccine adjuvant in a variety of species. Nano-11 is a versatile adjuvant that can be used for alternative routes of vaccination and in combination with other immunostimulatory molecules. This review discusses our current understanding of the mechanism of action of Nano-11 and its future potential applications in animal vaccines.

A split influenza vaccine formulated with a combination adjuvant composed of alpha-d-glucan nanoparticles and a STING agonist elicits cross-protective immunity in pigs

“…Plant-derived phytoglycogen (PG) is a densely branched dendrimer-like a- d -glucan that forms nanoparticle structures. Two simple chemical modifications of corn-derived PG create positively charged, amphiphilic nanoparticles, known as Nano-11, that stimulate immune responses when used as vaccine adjuvant in a variety of species [ 8 , 9 ]. Nano-11 is a versatile adjuvant that can be used for alternative routes of vaccination and in combination with other immunostimulatory molecules.…”

Characterization of the Efficacy of a Split Swine Influenza A Virus Nasal Vaccine Formulated with a Nanoparticle/STING Agonist Combination Adjuvant in Conventional Pigs

“…Earlier publications from our group demonstrated the significance of corn-based cationic alpha-D-glucan nanoparticles (Nano11) in mice and pigs, showing increased immunogenicity to vaccine antigens in mice and reduced virus load in pigs [13]. The intrinsic adjuvanticity of Nano11 can be augmented via the adsorption of suitable adjuvants such as Toll-like receptor-3 (TLR3) agonist poly(I:C) and the STING-agonist cyclic-di-adenosine monophosphate (AMP) [13]. Inactivated split IAV vaccines are more efficacious than inactivated whole virus vaccines [14][15][16][17].…”

“…Nanoparticle-based vaccines offer many advantages leading to efficacious antigen presentation and robust immunogenicity [11,12]. Earlier publications from our group demonstrated the significance of corn-based cationic alpha-D-glucan nanoparticles (Nano11) in mice and pigs, showing increased immunogenicity to vaccine antigens in mice and reduced virus load in pigs [13]. The intrinsic adjuvanticity of Nano11 can be augmented via the adsorption of suitable adjuvants such as Toll-like receptor-3 (TLR3) agonist poly(I:C) and the STING-agonist cyclic-di-adenosine monophosphate (AMP) [13].…”

Gas-Phase Functionalization of Phytoglycogen Nanoparticles and the Role of Reagent Structure in the Formation of Self-Limiting Hydrophobic Shells

“…For example, cationic groups can be introduced through a reaction with 3-chloro-2-hydroxypropyl trimethylammonium chloride. 1,16 This positive charge enables PhG NPs to act as vaccine adjuvants 16,17 and to deliver payloads such as dsRNA 18,19 and selenium 6 to cells, although the mechanism of cellular uptake remains unclear. 1 Amphiphilic modifications of PhG NPs have also been explored to improve encapsulation and delivery of lipophilic pharmaceuticals, 5,20 anticancer agents, 21,22 and natural products such as curcumin.…”

“…The high density of hydroxyl groups in PhG also facilitates diverse chemical modifications, resulting in modulated properties. For example, cationic groups can be introduced through a reaction with 3-chloro-2-hydroxypropyl trimethylammonium chloride. , This positive charge enables PhG NPs to act as vaccine adjuvants , and to deliver payloads such as dsRNA , and selenium to cells, although the mechanism of cellular uptake remains unclear . Amphiphilic modifications of PhG NPs have also been explored to improve encapsulation and delivery of lipophilic pharmaceuticals, , such as anticancer agents, , and natural products such as curcumin. , Some anionic modifications to PhG have resulted in superior uptake of cationic peptides .…”