Oral delivery of a dsRNA-Phytoglycogen nanoparticle complex enhances both local and systemic innate immune responses in rainbow trout

Samms, Kayla; Alkie, Tamiru Negash; Jenik, Kristof; Jong, Jondavid de; Klinger, Karl; DeWitte‐Orr, Stephanie J.

doi:10.1016/j.fsi.2021.12.038

Cited by 8 publications

(5 citation statements)

References 28 publications

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“…Interestingly, our methodology of two-step chemical modification confers intrinsic immunostimulatory activity to Nano-11 which appears to be unique to this preparation. Cationic alpha- d -glucan nanoparticles generated via different chemical modifications had no immunostimulatory activity by themselves [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Background Swine influenza A viruses (SwIAVs) pose an economic and pandemic threat, and development of novel effective vaccines is of critical significance. We evaluated the performance of split swine influenza A virus (SwIAV) H1N2 antigens with a plant-derived nanoparticle adjuvant alone (Nano-11) [Nano11-SwIAV] or in combination with the synthetic stimulator of interferon genes (STING) agonist ADU-S100 (NanoS100-SwIAV). Specific pathogen free (SPF) pigs were vaccinated twice via intramuscular (IM) or intradermal (ID) routes and challenged with a virulent heterologous SwIAV H1N1-OH7 virus. Results Animals vaccinated IM or ID with NanoS100-SwIAV had significantly increased cross-reactive IgG and IgA titers in serum, nasal secretion and bronchoalveolar lavage fluid at day post challenge 6 (DPC6). Furthermore, NanoS100-SwIAV ID vaccinates, even at half the vaccine dose compared to their IM vaccinated counterparts, had significantly increased frequencies of CXCL10+ myeloid cells in the tracheobronchial lymph nodes (TBLN), and IFNγ+ effector memory T-helper/memory cells, IL-17A+ total T-helper/memory cells, central and effector memory T-helper/memory cells, IL-17A+ total cytotoxic T-lymphocytes (CTLs), and early effector CTLs in blood compared with the Nano11-SwIAV group demonstrating a potential dose-sparing effect and induction of a strong IL-17A+ T-helper/memory (Th17) response in the periphery. However, the frequencies of IFNγ+ late effector CTLs and effector memory T-helper/memory cells, IL-17A+ total CTLs, late effector CTLs, and CXCL10+ myeloid cells in blood, as well as lung CXCL10+ plasmacytoid dendritic cells were increased in NanoS100-SwIAV IM vaccinated pigs. Increased expression of IL-4 and IL-6 mRNA was observed in TBLN of Nano-11 based IM vaccinates following challenge. Furthermore, the challenge virus load in the lungs and nasal passage was undetectable in NanoS100-SwIAV IM vaccinates by DPC6 along with reduced macroscopic lung lesions and significantly higher virus neutralization titers in lungs at DPC6. However, NanoS100-SwIAV ID vaccinates exhibited significant reduction of challenge virus titers in nasal passages and a remarkable reduction of challenge virus in lungs. Conclusions Despite vast genetic difference (77% HA gene identity) between the H1N2 and H1N1 SwIAV, the NanoS100 adjuvanted vaccine elicited cross protective cell mediated immune responses, suggesting the potential role of this combination adjuvant in inducing cross-protective immunity in pigs. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Recently, trained immunity has been demonstrated in porcine monocytes in vitro ( 26 ). Recent studies have shown that cationic phytoglycogen nanoparticles can be used as a delivery vehicle for the TLR3 agonist poly(I:C) and induces activation of innate immune cells following oral delivery in rainbow trout ( 14 ). The peripheral triggering of innate immune memory in mouse alveolar macrophages following an adenoviral respiratory infection in the mucosal tissues has also been reported and this was facilitated by IFN-γ generated by CD8 + T-cells.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, we also corroborate these findings in pigs vaccinated with Nano-11 adsorbed inactivated swine influenza virus antigen administered intranasally ( 12 , 13 ). Furthermore, new studies in rainbow trout also proved that PG-derived cationic nanopartcles are safe and efficacious delivery platforms ( 7 , 14 ). Initial in vitro characterization of antigen adsorbed Nano-11 nanoparticles revealed that the protein release pattern during the first 24 hours was ranging from 3-10% depending on the Nano-11 to inactivated swine influenza A whole virus antigen ratios.…”

Section: Physical Characteristics Of Nano-11mentioning

confidence: 99%

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

et al. 2022

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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.

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“…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.…”

Section: ■ Introductionmentioning

confidence: 99%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

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

Phillips,

Lankone,

O’Hagan

et al. 2024

Biomacromolecules

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A suite of acyl chloride structural isomers (C 6 H 11 OCl) was used to effect gas-phase esterification of starch-based phytoglycogen nanoparticles (PhG NPs). The surface degree of substitution (DS) was quantified using X-ray photoelectron spectroscopy, while the overall DS was quantified using 1 H NMR spectroscopy. Gas-phase modification initiates at the NP surface, with the extent of surface and overall esterification determined by both the reaction time and the steric footprint of the acyl chloride reagent. The less sterically hindered acyl chlorides diffuse fully into the NP interior, while the branched isomers are restricted to the near-surface region and form self-limiting hydrophobic shells, with shell thicknesses decreasing with increasing steric footprint. These differences in substitution were also reflected in the solubility of the NPs, with water solubility systematically decreasing with increasing DS. The ability to separately control both the surface and overall degree of functionalization and thereby form thin hydrophobic shells has significant implications for the development of polysaccharide-based biopolymers as nanocarrier delivery systems.

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Oral delivery of a dsRNA-Phytoglycogen nanoparticle complex enhances both local and systemic innate immune responses in rainbow trout

Cited by 8 publications

References 28 publications

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

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

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

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

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