Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer
Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. H...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Polymers |
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| Online Access: | https://www.mdpi.com/2073-4360/14/24/5466 |
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| author | Changcai Teng Xiongyan Meng Yeqin Hu Hongzhao Mao Huiting Li Jing Yang Tiantian Sun Shuai Meng Chengli Zong |
| author_facet | Changcai Teng Xiongyan Meng Yeqin Hu Hongzhao Mao Huiting Li Jing Yang Tiantian Sun Shuai Meng Chengli Zong |
| author_sort | Changcai Teng |
| collection | DOAJ |
| description | Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine’s immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-Blue<sup>TM</sup> hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant. |
| first_indexed | 2024-03-09T15:56:24Z |
| format | Article |
| id | doaj.art-5aea92c613434265b7127c2d78b22523 |
| institution | Directory Open Access Journal |
| issn | 2073-4360 |
| language | English |
| last_indexed | 2024-03-09T15:56:24Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Polymers |
| spelling | doaj.art-5aea92c613434265b7127c2d78b225232023-11-24T17:32:37ZengMDPI AGPolymers2073-43602022-12-011424546610.3390/polym14245466Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD TrimerChangcai Teng0Xiongyan Meng1Yeqin Hu2Hongzhao Mao3Huiting Li4Jing Yang5Tiantian Sun6Shuai Meng7Chengli Zong8Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaMAXVAX Bio-tech Co., Ltd., Chengdu 610200, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaSmall synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine’s immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-Blue<sup>TM</sup> hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.https://www.mdpi.com/2073-4360/14/24/5466adjuvantsmannoseTLR7/8 agonistimmune responsescytokinesantibody |
| spellingShingle | Changcai Teng Xiongyan Meng Yeqin Hu Hongzhao Mao Huiting Li Jing Yang Tiantian Sun Shuai Meng Chengli Zong Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer Polymers adjuvants mannose TLR7/8 agonist immune responses cytokines antibody |
| title | Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer |
| title_full | Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer |
| title_fullStr | Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer |
| title_full_unstemmed | Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer |
| title_short | Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer |
| title_sort | self assembled tlr7 8 agonist mannose conjugate as an effective vaccine adjuvant for sars cov 2 rbd trimer |
| topic | adjuvants mannose TLR7/8 agonist immune responses cytokines antibody |
| url | https://www.mdpi.com/2073-4360/14/24/5466 |
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