tetano
Editor, Senior Moderator
Adv Healthc Mater
. 2024 Sep 25:e2401650.
doi: 10.1002/adhm.202401650. Online ahead of print. Constructing the cGAMP-Aluminum Nanoparticles as a Vaccine Adjuvant-Delivery System (VADS) for Developing the Efficient Pulmonary COVID-19 Subunit Vaccines
Ning Wang[SUP] 1 2 [/SUP], Can Wang[SUP] 2 3 [/SUP], Chunliu Wei[SUP] 2 [/SUP], Minnan Chen[SUP] 2 [/SUP], Yuhao Gao[SUP] 2 [/SUP], Yuxi Zhang[SUP] 2 [/SUP], Ting Wang[SUP] 2 [/SUP]
Affiliations
The cGAMP-aluminum nanoparticles (CAN) are engineered as a vaccine adjuvant-delivery system to carry mixed RBD (receptor-binding domain) of the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variant for developing bivalent pulmonary coronavirus disease 2019 (COVID-19) vaccines (biRBD-CAN). High phosphophilicity/adsorptivity made intrapulmonary CAN instantly form the pulmonary ingredient-coated CAN (piCAN) to possess biomimetic features enhancing biocompatibility. In vitro biRBD-CAN sparked APCs (antigen-presenting cells) to mature and make extra reactive oxygen species, engendered lysosome escape effects and enhanced proteasome activities. Through activating the intracellular stimulator of interferon genes (STING) and nucleotide-binding domain and leucine-rich repeat and pyrin domain containing proteins 3 (NALP3) inflammasome pathways to exert synergy between cGAMP and AN, biRBD-CAN stimulated APCs to secret cytokines favoring mixed Th1/Th2 immunoresponses. Mice bearing twice intrapulmonary biRBD-CAN produced high levels of mucosal antibodies, the long-lasting systemic antibodies, and potent cytotoxic T lymphocytes which efficiently erased cells displaying cognate epitopes. Notably, biRBD-CAN existed in mouse lungs and different lymph nodes for at least 48 h, unveiling their sustained immunostimulatory activity as the main mechanism underlying the long-lasting immunity and memory. Hamsters bearing twice intrapulmonary biRBD-CAN developed high resistance to pseudoviral challenges performed using different recombinant strains including the ones with distinct SARS-CoV-2-spike mutations. Thus, biRBD-CAN as a broad-spectrum pulmonary COVID-19 vaccine candidate may provide a tool for controlling the emerging SARS-CoV-2 variants.
Keywords: STING pathway; immune memory; long‐lived plasma cell; mucosal immunity; vaccine adjuvant‐delivery system.
Ning Wang[SUP] 1 2 [/SUP], Can Wang[SUP] 2 3 [/SUP], Chunliu Wei[SUP] 2 [/SUP], Minnan Chen[SUP] 2 [/SUP], Yuhao Gao[SUP] 2 [/SUP], Yuxi Zhang[SUP] 2 [/SUP], Ting Wang[SUP] 2 [/SUP]
Affiliations
The cGAMP-aluminum nanoparticles (CAN) are engineered as a vaccine adjuvant-delivery system to carry mixed RBD (receptor-binding domain) of the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variant for developing bivalent pulmonary coronavirus disease 2019 (COVID-19) vaccines (biRBD-CAN). High phosphophilicity/adsorptivity made intrapulmonary CAN instantly form the pulmonary ingredient-coated CAN (piCAN) to possess biomimetic features enhancing biocompatibility. In vitro biRBD-CAN sparked APCs (antigen-presenting cells) to mature and make extra reactive oxygen species, engendered lysosome escape effects and enhanced proteasome activities. Through activating the intracellular stimulator of interferon genes (STING) and nucleotide-binding domain and leucine-rich repeat and pyrin domain containing proteins 3 (NALP3) inflammasome pathways to exert synergy between cGAMP and AN, biRBD-CAN stimulated APCs to secret cytokines favoring mixed Th1/Th2 immunoresponses. Mice bearing twice intrapulmonary biRBD-CAN produced high levels of mucosal antibodies, the long-lasting systemic antibodies, and potent cytotoxic T lymphocytes which efficiently erased cells displaying cognate epitopes. Notably, biRBD-CAN existed in mouse lungs and different lymph nodes for at least 48 h, unveiling their sustained immunostimulatory activity as the main mechanism underlying the long-lasting immunity and memory. Hamsters bearing twice intrapulmonary biRBD-CAN developed high resistance to pseudoviral challenges performed using different recombinant strains including the ones with distinct SARS-CoV-2-spike mutations. Thus, biRBD-CAN as a broad-spectrum pulmonary COVID-19 vaccine candidate may provide a tool for controlling the emerging SARS-CoV-2 variants.
Keywords: STING pathway; immune memory; long‐lived plasma cell; mucosal immunity; vaccine adjuvant‐delivery system.
. 2024 Sep 25:e2401650.
doi: 10.1002/adhm.202401650. Online ahead of print. Constructing the cGAMP-Aluminum Nanoparticles as a Vaccine Adjuvant-Delivery System (VADS) for Developing the Efficient Pulmonary COVID-19 Subunit Vaccines
Ning Wang[SUP] 1 2 [/SUP], Can Wang[SUP] 2 3 [/SUP], Chunliu Wei[SUP] 2 [/SUP], Minnan Chen[SUP] 2 [/SUP], Yuhao Gao[SUP] 2 [/SUP], Yuxi Zhang[SUP] 2 [/SUP], Ting Wang[SUP] 2 [/SUP]
Affiliations
- PMID: 39319481
- DOI: 10.1002/adhm.202401650
The cGAMP-aluminum nanoparticles (CAN) are engineered as a vaccine adjuvant-delivery system to carry mixed RBD (receptor-binding domain) of the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variant for developing bivalent pulmonary coronavirus disease 2019 (COVID-19) vaccines (biRBD-CAN). High phosphophilicity/adsorptivity made intrapulmonary CAN instantly form the pulmonary ingredient-coated CAN (piCAN) to possess biomimetic features enhancing biocompatibility. In vitro biRBD-CAN sparked APCs (antigen-presenting cells) to mature and make extra reactive oxygen species, engendered lysosome escape effects and enhanced proteasome activities. Through activating the intracellular stimulator of interferon genes (STING) and nucleotide-binding domain and leucine-rich repeat and pyrin domain containing proteins 3 (NALP3) inflammasome pathways to exert synergy between cGAMP and AN, biRBD-CAN stimulated APCs to secret cytokines favoring mixed Th1/Th2 immunoresponses. Mice bearing twice intrapulmonary biRBD-CAN produced high levels of mucosal antibodies, the long-lasting systemic antibodies, and potent cytotoxic T lymphocytes which efficiently erased cells displaying cognate epitopes. Notably, biRBD-CAN existed in mouse lungs and different lymph nodes for at least 48 h, unveiling their sustained immunostimulatory activity as the main mechanism underlying the long-lasting immunity and memory. Hamsters bearing twice intrapulmonary biRBD-CAN developed high resistance to pseudoviral challenges performed using different recombinant strains including the ones with distinct SARS-CoV-2-spike mutations. Thus, biRBD-CAN as a broad-spectrum pulmonary COVID-19 vaccine candidate may provide a tool for controlling the emerging SARS-CoV-2 variants.
Keywords: STING pathway; immune memory; long‐lived plasma cell; mucosal immunity; vaccine adjuvant‐delivery system.
Ning Wang[SUP] 1 2 [/SUP], Can Wang[SUP] 2 3 [/SUP], Chunliu Wei[SUP] 2 [/SUP], Minnan Chen[SUP] 2 [/SUP], Yuhao Gao[SUP] 2 [/SUP], Yuxi Zhang[SUP] 2 [/SUP], Ting Wang[SUP] 2 [/SUP]
Affiliations
- PMID: 39319481
- DOI: 10.1002/adhm.202401650
The cGAMP-aluminum nanoparticles (CAN) are engineered as a vaccine adjuvant-delivery system to carry mixed RBD (receptor-binding domain) of the original severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new variant for developing bivalent pulmonary coronavirus disease 2019 (COVID-19) vaccines (biRBD-CAN). High phosphophilicity/adsorptivity made intrapulmonary CAN instantly form the pulmonary ingredient-coated CAN (piCAN) to possess biomimetic features enhancing biocompatibility. In vitro biRBD-CAN sparked APCs (antigen-presenting cells) to mature and make extra reactive oxygen species, engendered lysosome escape effects and enhanced proteasome activities. Through activating the intracellular stimulator of interferon genes (STING) and nucleotide-binding domain and leucine-rich repeat and pyrin domain containing proteins 3 (NALP3) inflammasome pathways to exert synergy between cGAMP and AN, biRBD-CAN stimulated APCs to secret cytokines favoring mixed Th1/Th2 immunoresponses. Mice bearing twice intrapulmonary biRBD-CAN produced high levels of mucosal antibodies, the long-lasting systemic antibodies, and potent cytotoxic T lymphocytes which efficiently erased cells displaying cognate epitopes. Notably, biRBD-CAN existed in mouse lungs and different lymph nodes for at least 48 h, unveiling their sustained immunostimulatory activity as the main mechanism underlying the long-lasting immunity and memory. Hamsters bearing twice intrapulmonary biRBD-CAN developed high resistance to pseudoviral challenges performed using different recombinant strains including the ones with distinct SARS-CoV-2-spike mutations. Thus, biRBD-CAN as a broad-spectrum pulmonary COVID-19 vaccine candidate may provide a tool for controlling the emerging SARS-CoV-2 variants.
Keywords: STING pathway; immune memory; long‐lived plasma cell; mucosal immunity; vaccine adjuvant‐delivery system.