Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity
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 ing...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/13/10/1569 |
| _version_ | 1797513388360728576 |
|---|---|
| author | Chih-An Lin Hui-Min Ho Parthiban Venkatesan Chiung-Yi Huang Yu-Jhen Cheng Yu-Hsing Lin Hua-Yang Lin Tzu-Yang Chen Ming-Hsi Huang Ping-Shan Lai |
| author_facet | Chih-An Lin Hui-Min Ho Parthiban Venkatesan Chiung-Yi Huang Yu-Jhen Cheng Yu-Hsing Lin Hua-Yang Lin Tzu-Yang Chen Ming-Hsi Huang Ping-Shan Lai |
| author_sort | Chih-An Lin |
| collection | DOAJ |
| description | 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 AlPO<sub>4</sub> 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. |
| first_indexed | 2024-03-10T06:16:51Z |
| format | Article |
| id | doaj.art-0573a835337448b38ce60e67c722bcc0 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T06:16:51Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0573a835337448b38ce60e67c722bcc02023-11-22T19:37:43ZengMDPI AGPharmaceutics1999-49232021-09-011310156910.3390/pharmaceutics13101569Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated ImmunityChih-An Lin0Hui-Min Ho1Parthiban Venkatesan2Chiung-Yi Huang3Yu-Jhen Cheng4Yu-Hsing Lin5Hua-Yang Lin6Tzu-Yang Chen7Ming-Hsi Huang8Ping-Shan Lai9Ph.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City 402204, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli City 350401, TaiwanDepartment of Chemistry, National Chung Hsing University, Taichung City 402204, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli City 350401, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli City 350401, TaiwanPreclinical Development Research Department, Holy Stone Healthcare Co., Ltd., Hsinchu 114066, TaiwanPreclinical Development Research Department, Holy Stone Healthcare Co., Ltd., Hsinchu 114066, TaiwanDepartment of Chemistry, National Chung Hsing University, Taichung City 402204, TaiwanPh.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City 402204, TaiwanPh.D. Program in Tissue Engineering and Regenerative Medicine, National Chung Hsing University, Taichung City 402204, TaiwanClinical 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 AlPO<sub>4</sub> 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.https://www.mdpi.com/1999-4923/13/10/1569hyaluronic acidcholesterolsqualenenanoemulsionvaccine adjuvantsPEG-free formulation |
| spellingShingle | Chih-An Lin Hui-Min Ho Parthiban Venkatesan Chiung-Yi Huang Yu-Jhen Cheng Yu-Hsing Lin Hua-Yang Lin Tzu-Yang Chen Ming-Hsi Huang Ping-Shan Lai Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity Pharmaceutics hyaluronic acid cholesterol squalene nanoemulsion vaccine adjuvants PEG-free formulation |
| title | Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity |
| title_full | Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity |
| title_fullStr | Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity |
| title_full_unstemmed | Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity |
| title_short | Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity |
| title_sort | hyaluronic acid glycine cholesterol conjugate based nanoemulsion as a potent vaccine adjuvant for t cell mediated immunity |
| topic | hyaluronic acid cholesterol squalene nanoemulsion vaccine adjuvants PEG-free formulation |
| url | https://www.mdpi.com/1999-4923/13/10/1569 |
| work_keys_str_mv | AT chihanlin hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT huiminho hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT parthibanvenkatesan hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT chiungyihuang hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT yujhencheng hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT yuhsinglin hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT huayanglin hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT tzuyangchen hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT minghsihuang hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity AT pingshanlai hyaluronicacidglycinecholesterolconjugatebasednanoemulsionasapotentvaccineadjuvantfortcellmediatedimmunity |