Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

Pietà, Anna Dalla; Carpanese, Debora; Grigoletto, Antonella; Tosi, Anna; Santa, Silvia Dalla; Pedersen, Gabriel Kristian; Christensen, Dennis; Meléndez‐Alafort, Laura; Barbieri, Vito; Benedictis, Paola De; Pasut, Gianfranco; Montagner, Isabella Monia; Rosato, Antonio

doi:10.1038/s41423-021-00667-y

Cited by 17 publications

(21 citation statements)

References 52 publications

(20 reference statements)

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“…Thus, we speculate the generation of LMW HA fragments from the degradation of HACH can further activate DCs and enhance antigen recognition and antigen presentation to Th cells. Of note, Pietà et al also report similar results on HA-bioconjugated OVA, and they indicate that HA also stimulates a T cell immunity, especially Th1 immune response, and leads to the generation of an OVA-specific cytotoxic response [51]. Detailed investigations are ongoing at our laboratory.…”

Section: Modulation Of the Adjuvant-mediated T Cell Activationsupporting

confidence: 53%

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity

Lin

Venkatesan

et al. 2021

Pharmaceutics

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Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.% cholesterol has good water dispersity and can serve as an emulsifier to stabilize the squalene/water interfaces, yielding a milky white and isotropic emulsion (SQ@HACH) after being passed through a high-shear microfluidizer. Our results show that SQ@HACH particles possessed a unimodal average hydrodynamic diameter of approximately 190 nm measured by dynamic light scattering and exhibited good stability upon storage at 4 °C and 37 °C for over 20 weeks. The results of immunogenicity using a mouse model with ovalbumin (OVA) as the antigen revealed that SQ@HACH significantly enhanced antigen-specific immune responses, including the polarization of IgG antibodies, the cytokine secretions of T cells, and enhancement of cytotoxic T lymphocyte (CTL) activation. Moreover, SQ@HACH revealed lower local inflammation and rapidly absorbing properties compared with AlPO4 after intramuscular injection in vivo, indicating the potential functions of the HA-derived conjugate as an excipient in vaccine formulations for enhancement of T cell-mediated immunity.

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Section: Modulation Of the Adjuvant-mediated T Cell Activationsupporting

confidence: 53%

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity

Lin

Venkatesan

et al. 2021

Pharmaceutics

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“…It belongs to the group of compounds called glycosaminoglycans (GAGs) [ 4 ]. The polymer’s molecule is made of D-glucuronic acid and N-acetylglucosamine ( Figure 1 ), connected by alternating glycosidic bonds β (1–4) and β (1–3) [ 5 ]. However, hyaluronan differs from the others GAGs.…”

Section: Introductionmentioning

confidence: 99%

Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models

et al. 2021

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This work investigated the potential of a novel formulation of eye drops containing a non-steroidal anti-inflammatory drug—choline salicylate (CS)—and hyaluronic acid (HA). Thus, these drops may exert both anti-inflammatory and regenerative activity. The experiment was conducted through the careful characterization of physicochemical properties, stability, and quality of eye drops. Moreover, microbiological analysis, as well as penetration and cytotoxic studies, were performed. The UV, HPLC-UV, and HPLC-MS/MS methods were used to determine the purity and stability of CS. The penetration rate of CS was assessed using a hydrophilic membrane and ex vivo porcine cornea model. Additionally, the cytotoxic effects were evaluated using the SIRC cell line. The interaction between HA and CS was tested using size-exclusion chromatography and IR spectrophotometry. As a result, HA increased the viscosity of the drops, which prolonged their contact with the ocular surface, thus ensuring more effective penetration of CS into the corneal structure. After long-term storage, an interaction in the pharmaceutical phase between CS and HA was observed. However, this interaction did not affect the viability of rabbit corneal cells. Our findings showed that eye drops with CS and HA, stored at 2–8 °C in light-protected conditions, met the criteria of stability and safety.

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“…Notably, fluoresceinlabeled ovalbumin released from HA-based MAP diffused more rapidly than from CMCbased MAP and persisted in rat skin for a longer duration (48 hours vs. 24 hours) (33), demonstrating an adjuvant function. Indeed, HA acts as an immunological adjuvant for protein-based vaccines (34,35). The chemical bonding of HA to antigens stimulated strong and enduring humoral responses without requiring additional immunostimulatory compounds, leading to reduced booster needs and enabling antigen dose conservation 1 2 (35).…”

Section: Discussionmentioning

confidence: 99%

Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice

Kim,

Shin,

Ferrari

et al. 2023

Preprint

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The COVID-19 pandemic has underscored the pressing need for safe and effective booster vaccines, particularly in considering the emergence of new SARS-CoV-2 variants and addressing vaccine distribution inequalities. Dissolving microneedle array patches (MAP) offer a promising delivery method, enhancing immunogenicity and improving accessibility through the skin’s immune potential. In this study, we evaluated a microneedle array patch-based S1 subunit protein COVID-19 vaccine candidate, which comprised a bivalent formulation targeting the Wuhan and Beta variant alongside a monovalent Delta variant spike proteins in a murine model. Notably, the second boost of homologous bivalent MAP-S1(WU+Beta) induced a 15.7-fold increase in IgG endpoint titer, while the third boost of heterologous MAP-S1RS09Delta yielded a more modest 1.6-fold increase. Importantly, this study demonstrated that the administration of four doses of the MAP vaccine induced robust and long-lasting immune responses, persisting for at least 80 weeks. These immune responses encompassed various IgG isotypes and remained statistically significant for one year. Furthermore, neutralizing antibodies against multiple SARS-CoV-2 variants were generated, with comparable responses observed against the Omicron variant. Overall, these findings emphasize the potential of MAP-based vaccines as a promising strategy to combat the evolving landscape of COVID-19 and to deliver a safe and effective booster vaccine worldwide.

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Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

Cited by 17 publications

References 52 publications

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity

Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity

Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models

Fourth dose of Microneedle Array Patch of SARS-CoV-2 S1 Protein Subunit Vaccine Elicits Robust Long-lasting Humoral Responses in mice

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