Abstract
Objective
To create a novel subunit vaccine that used AuNPs as carriers to enhance immune responses in mice against recombinant classical swine fever virus E2 protein (CSFV E2).
Results
Gold nanoparticles (AuNPs) were successfully coupled to the E2 protein and formed stable particle complexes called E2 conjugated AuNPs (E2–AuNPs). In vitro studies have shown that the E2–AuNPs complex has the same immunogenicity as the E2 protein, and AuNPs can promote the phagocytosis of the E2 protein by antigen-presenting cells (APCs). In vivo results of BALB/c mice showed that the antibody levels, lymphocyte proliferation index, IFN-γ and IL-10 cytokines induced by E2–AuNPs were relatively higher than those of E2 or AuNPs group.
Conclusions
This finding demonstrated the potential of using AuNPs as a carrier to enhance the body's immune response for developing CSFV subunit vaccines. This model also contributes to the development of other flavivirus subunit vaccines, such as hepatitis C virus (HCV) and bovine viral diarrhea virus (BVDV).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Explore related subjects
Discover the latest articles and news from researchers in related subjects, suggested using machine learning.References
Aborig M et al (2019) Biodistribution and physiologically-based pharmacokinetic modeling of gold nanoparticles in mice with interspecies extrapolation. Pharmaceutics 11:179. https://doi.org/10.3390/pharmaceutics11040179
Carabineiro SAC (2017) Applications of gold nanoparticles in nanomedicine: recent advances in vaccines. Molecules 22:857. https://doi.org/10.3390/molecules22050857
Chattopadhyay S, Chen JY, Chen HW, Hu CJ (2017) Nanoparticle vaccines adopting virus-like features for enhanced immune potentiation. Nanotheranostics 1:244–260. https://doi.org/10.7150/ntno.19796
Chen YS, Hung YC, Lin WH, Huang GS (2010) Assessment of gold nanoparticles as a size-dependent vaccine carrier for enhancing the antibody response against synthetic foot-and-mouth disease virus peptide. Nanotechnology 21:195101. https://doi.org/10.1088/0957-4484/21/19/195101
Cheung WH et al (2009) Conjugation of latent membrane protein (LMP)-2 epitope to gold nanoparticles as highly immunogenic multiple antigenic peptides for induction of Epstein-Barr virus-specific cytotoxic T-lymphocyte responses in vitro. Bioconjug Chem 20:24–31. https://doi.org/10.1021/bc800167q
Dakterzada F, Mohabati Mobarez A, Habibi Roudkenar M, Mohsenifar A (2016) Induction of humoral immune response against Pseudomonas aeruginosa flagellin(1–161) using gold nanoparticles as an adjuvant. Vaccine 34:1472–1479. https://doi.org/10.1016/j.vaccine.2016.01.041
Dhur A, Galan P, Preziosi P, Hercberg S (1991) Lymphocyte subpopulations in the thymus, lymph nodes and spleen of iron-deficient and rehabilitated mice. J Nutr 121:1418–1424. https://doi.org/10.1093/jn/121.9.1418
Ding P et al (2017) Nanoparticle orientationally displayed antigen epitopes improve neutralizing antibody level in a model of porcine circovirus type 2. Int J Nanomedicine 12:5239–5254. https://doi.org/10.2147/ijn.s140789
Duncan B, Kim C, Rotello VM (2010) Gold nanoparticle platforms as drug and biomacromolecule delivery systems. J Control Release 148:122–127. https://doi.org/10.1016/j.jconrel.2010.06.004
Gregory AE, Williamson ED, Prior JL, Butcher WA, Thompson IJ, Shaw AM, Titball RW (2012) Conjugation of Y. pestis F1-antigen to gold nanoparticles improves immunogenicity. Vaccine 30:6777–6782. https://doi.org/10.1016/j.vaccine.2012.09.021
Haiss W, Thanh NT, Aveyard J, Fernig DG (2007) Determination of size and concentration of gold nanoparticles from UV-vis spectra. Anal Chem 79:4215–4221. https://doi.org/10.1021/ac0702084
Ji W, Guo Z, Ding NZ, He CQ (2015) Studying classical swine fever virus: making the best of a bad virus. Virus Res 197:35–47. https://doi.org/10.1016/j.virusres.2014.12.006
Kimling J, Maier M, Okenve B, Kotaidis V, Ballot H, Plech A (2006) Turkevich method for gold nanoparticle synthesis revisited. J Phys Chem B 110:15700–15707. https://doi.org/10.1021/jp061667w
Lopez-Sagaseta J, Malito E, Rappuoli R, Bottomley MJ (2016) Self-assembling protein nanoparticles in the design of vaccines. Comput Struct Biotechnol J 14:58–68. https://doi.org/10.1016/j.csbj.2015.11.001
Lou S, Ye JY, Li KQ, Wu A (2012) A gold nanoparticle-based immunochromatographic assay: the influence of nanoparticulate size. Analyst 137:1174–1181. https://doi.org/10.1039/c2an15844b
Marques Neto LM, Kipnis A, Junqueira-Kipnis AP (2017) Role of metallic nanoparticles in vaccinology: implications for infectious disease vaccine development. Front Immunol 8:239. https://doi.org/10.3389/fimmu.2017.00239
Reddy ST et al (2007) Exploiting lymphatic transport and complement activation in nanoparticle vaccines. Nat Biotechnol 25:1159–1164. https://doi.org/10.1038/nbt1332
Salazar-Gonzalez JA, Gonzalez-Ortega O, Rosales-Mendoza S (2015) Gold nanoparticles and vaccine development. Expert Rev Vaccines 14:1197–1211. https://doi.org/10.1586/14760584.2015.1064772
Shukla R, Bansal V, Chaudhary M, Basu A, Bhonde RR, Sastry M (2005) Biocompatibility of gold nanoparticles and their endocytotic fate inside the cellular compartment: a microscopic overview. Langmuir 21:10644–10654. https://doi.org/10.1021/la0513712
Staroverov SA, Vidyasheva IV, Gabalov KP, Vasilenko OA, Laskavyi VN, Dykman LA (2011) Immunostimulatory effect of gold nanoparticles conjugated with transmissible gastroenteritis virus. Bull Exp Biol Med 151:436–439
Stone JW, Thornburg NJ, Blum DL, Kuhn SJ, Wright DW, Crowe JE Jr (2013) Gold nanorod vaccine for respiratory syncytial virus. Nanotechnology 24:295102. https://doi.org/10.1088/0957-4484/24/29/295102
Tao W, Gill HS (2015) M2e-immobilized gold nanoparticles as influenza A vaccine: role of soluble M2e and longevity of protection. Vaccine 33:2307–2315. https://doi.org/10.1016/j.vaccine.2015.03.063
Tao W, Ziemer KS, Gill HS (2014) Gold nanoparticle-M2e conjugate coformulated with CpG induces protective immunity against influenza A virus. Nanomedicine (Lond) 9:237–251. https://doi.org/10.2217/nnm.13.58
Walkey CD, Chan WC (2012) Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment. Chem Soc Rev 41:2780–2799. https://doi.org/10.1039/c1cs15233e
Wang Y et al (2016) Construction and Immunological Evaluation of CpG-Au@HBc Virus-Like Nanoparticles as a Potential Vaccine. Nanoscale Res Lett 11:338. https://doi.org/10.1186/s11671-016-1554-y
Zhang H et al (2014) Glycoprotein E2 of classical swine fever virus expressed by baculovirus induces the protective immune responses in rabbits. Vaccine 32:6607–6613. https://doi.org/10.1016/j.vaccine.2014.10.003
Zhao L, Seth A, Wibowo N, Zhao CX, Mitter N, Yu C, Middelberg AP (2014) Nanoparticle vaccines. Vaccine 32:327–337. https://doi.org/10.1016/j.vaccine.2013.11.069
Acknowledgements
The author is grateful to Ruiqin Li and Xiaokang Lu (Henan University of Chinese Medicine) for technical assistance with TEM analysis. This work was funded by grants from the Science-Technology Foundation for Outstanding Young Scientists of Henan Academy of Agricultural Sciences (Grant no. 2018YQ29), the National Key Research and Development Program of China (2017YFD0501103, 2016YFD0500701, 2016YFD0500709), China Agriculture Research System (CARS-36).
Author information
Authors and Affiliations
Contributions
Gaiping Zhang, Qianyue Jin, Yafei Li and Peiyang Ding contributed to the study conception and design. Wen Zhou, Yongxiao Chai, Xufeng Li and Yao Wang helped with the animal experiments. Yafei Li wrote the manuscript and analysed the data. Qianyue Jin, Peiyang Ding checked and revised it. All authors read and approved the final manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Ethical approval
The animal experiments were carried out according to the Animal Experiment Committee of Henan Academy of Agricultural Sciences (Approval number SYXK 2014–0007). All animals received humane care in compliance with good animal practice according to the animal ethics procedures and guidelines of China.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Li, Y., Jin, Q., Ding, P. et al. Gold nanoparticles enhance immune responses in mice against recombinant classical swine fever virus E2 protein. Biotechnol Lett 42, 1169–1180 (2020). https://doi.org/10.1007/s10529-020-02853-w
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10529-020-02853-w