TY - JOUR
T1 - Highly stable gold nanoparticle-antigen conjugates with self-adjuvanting property for induction of robust antigen-specific immune responses
AU - Lin, Zih Yao
AU - Chen, Yu Hung
AU - Wu, Yan-Wei
AU - Chen, Mei Chin
N1 - Funding Information:
We thank the support from the laboratory animal center of NCKU and the technical services provided by the Bio-image Core Facility of the National Core Facility Program for Biopharmaceuticals , National Science and Technology Council , Taiwan. The authors also thank the financial support of the Ministry of Science and Technology of Taiwan (MOST 108–2314-B-006–074-MY3 and MOST 111-2628-B-006-012-MY3 ) and Wallace Academic Editing for editing this manuscript. We are gratefully acknowledge the use of ESCA000200 equipment (MOST 111-2731-M-006-001 ) belonging to the Core Facility Center of National Cheng Kung University .
Funding Information:
We thank the support from the laboratory animal center of NCKU and the technical services provided by the Bio-image Core Facility of the National Core Facility Program for Biopharmaceuticals, National Science and Technology Council, Taiwan. The authors also thank the financial support of the Ministry of Science and Technology of Taiwan (MOST 108–2314-B-006–074-MY3 and MOST 111-2628-B-006-012-MY3) and Wallace Academic Editing for editing this manuscript. We are gratefully acknowledge the use of ESCA000200 equipment (MOST 111-2731-M-006-001) belonging to the Core Facility Center of National Cheng Kung University. Method of in vitro OVA release study; XPS spectrum in Au 4f region for the GNP-PEG sample; size distribution and PDI of GNP, GNP-PEG and GNP-OVA before and after 12 months of storage in deionized water at 4 °C; photographs of GNP and GNP-OVA after storage in deionized water at 4 °C for 0, 6 and 12 months; photographs of GNP that was subjected to freeze-drying and rehydration processes; size distribution and PDI of GNP, GNP-PEG and GNP-OVA before and after lyophilization process; in vitro release profile of OVA from GNP-OVA and GNP-PEG/OVA in PBS. The authors declare that they have no competing interests.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/12
Y1 - 2022/12
N2 - Poor long-term stability and formation of irreversible aggregates when subjected to a freeze-drying process greatly limits the clinical application of gold nanoparticles (GNPs) as a vaccine carrier. In this study, we synthesized a GNP–antigen conjugate with high colloidal stability by using a thiolated polyethylene glycol (PEG) linker to conjugate a model antigen (ovalbumin; OVA) onto the GNP surface (i.e. GNP-OVA) and demonstrated this conjugate had self-adjuvanting properties to augment antigen-specific immune responses. The synthesized GNP had an average hydrodynamic size of 13.8 ± 2.1 nm (n = 3); after conjugation of OVA, the diameter increased to 28.6 ± 7.3 nm (n = 3). The obtained GNP-OVA can maintain a stable dispersion state in aqueous solutions for at least 12 months and withstand stresses during lyophilization without creating irreversible aggregates. Compared with OVA alone or a mixture of PEG-functionalized GNP (GNP-PEG) and OVA (i.e. GNP-PEG/OVA), the chemical conjugation of OVA onto GNP-PEG substantially increased antigen uptake and upregulated major histocompatibility complex class II expression in macrophages. This indicated that the GNP can function as not only an adjuvant to promote the phagocytic activity of macrophages but also a carrier to deliver the conjugated antigen into the immune cells for the enhancement of its antigen presentation capability. Importantly, OVA-specific immunoglobulin G levels in the mice immunized with GNP-OVA were 4.1 and 2.9 times higher than those in the mice injected with OVA and GNP-PEG/OVA, respectively. These results demonstrated that the GNP-antigen conjugate exhibited remarkable stability either in liquid or freeze-dried form, which makes it attractive for further pharmaceutical applications. Moreover, covalently linking antigens onto the GNP surface was enabled to enhance the immunogenicity of antigens and boost immune responses, showing the potential of the GNP conjugation strategy for vaccine development.
AB - Poor long-term stability and formation of irreversible aggregates when subjected to a freeze-drying process greatly limits the clinical application of gold nanoparticles (GNPs) as a vaccine carrier. In this study, we synthesized a GNP–antigen conjugate with high colloidal stability by using a thiolated polyethylene glycol (PEG) linker to conjugate a model antigen (ovalbumin; OVA) onto the GNP surface (i.e. GNP-OVA) and demonstrated this conjugate had self-adjuvanting properties to augment antigen-specific immune responses. The synthesized GNP had an average hydrodynamic size of 13.8 ± 2.1 nm (n = 3); after conjugation of OVA, the diameter increased to 28.6 ± 7.3 nm (n = 3). The obtained GNP-OVA can maintain a stable dispersion state in aqueous solutions for at least 12 months and withstand stresses during lyophilization without creating irreversible aggregates. Compared with OVA alone or a mixture of PEG-functionalized GNP (GNP-PEG) and OVA (i.e. GNP-PEG/OVA), the chemical conjugation of OVA onto GNP-PEG substantially increased antigen uptake and upregulated major histocompatibility complex class II expression in macrophages. This indicated that the GNP can function as not only an adjuvant to promote the phagocytic activity of macrophages but also a carrier to deliver the conjugated antigen into the immune cells for the enhancement of its antigen presentation capability. Importantly, OVA-specific immunoglobulin G levels in the mice immunized with GNP-OVA were 4.1 and 2.9 times higher than those in the mice injected with OVA and GNP-PEG/OVA, respectively. These results demonstrated that the GNP-antigen conjugate exhibited remarkable stability either in liquid or freeze-dried form, which makes it attractive for further pharmaceutical applications. Moreover, covalently linking antigens onto the GNP surface was enabled to enhance the immunogenicity of antigens and boost immune responses, showing the potential of the GNP conjugation strategy for vaccine development.
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U2 - 10.1016/j.colsurfb.2022.112897
DO - 10.1016/j.colsurfb.2022.112897
M3 - Article
C2 - 36215893
AN - SCOPUS:85139335954
SN - 0927-7765
VL - 220
JO - Colloids and Surfaces B: Biointerfaces
JF - Colloids and Surfaces B: Biointerfaces
M1 - 112897
ER -