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Amino-Modified Polymer Nanoparticles as Adjuvants to Activate the Complement System and to Improve Vaccine Efficacy in Vivo

  • Yong Pan
    Yong Pan
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
    University of Science and Technology of China, Hefei 230026, P. R. China
    More by Yong Pan
  • Yanxin Qi*
    Yanxin Qi
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
    Yanbian University Medical College, Yanji 133002, P. R. China
    *E-mail: [email protected] (Y.Q.).
    More by Yanxin Qi
  • Nannan Shao
    Nannan Shao
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
    University of Science and Technology of China, Hefei 230026, P. R. China
    More by Nannan Shao
  • Abegail C. Tadle
    Abegail C. Tadle
    Department of Chemistry, University of Southern California, Los Angeles, California 90089, United States
  • , and 
  • Yubin Huang*
    Yubin Huang
    State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
    University of Science and Technology of China, Hefei 230026, P. R. China
    *E-mail: [email protected] (Y.H.).
    More by Yubin Huang
Cite this: Biomacromolecules 2019, 20, 9, 3575–3583
Publication Date (Web):August 15, 2019
https://doi.org/10.1021/acs.biomac.9b00887
Copyright © 2019 American Chemical Society
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Supporting Info (1)»

Abstract

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Subunit vaccines are safer but often poorly immunogenic in comparison to traditional vaccines, and thus, adjuvants and delivery vehicles are needed to enhance the immune response. The complement system is a part of the innate immune system, which plays an important role in innate and adaptive immunity. Therefore, the activation of the complement system could be utilized as a potential strategy for vaccine applications. Herein, cysteamine hydrochloride was grafted onto a methoxy poly(ethylene glycol)-block-poly (allyl glycidyl ether)-block-poly(ε-caprolactone) copolymer to synthesize a triblock polymer mPEG5k-PAGE15(NH2)-PCL5k(TPCAH) with amino groups on the side chain. The positive charge of the amino groups could bind with the negatively charged protein (like ovalbumin (OVA)) to form a stable complex by electrostatic interaction. The triblock copolymer TPCAH we designed can easily self-assemble into polymer nanomicelles, and the size of the nanoparticles is similar to that of the pathogens, which was beneficial to the uptake by lymphocytes. Furthermore, the amino groups modified on the side chain can not only integrate with proteins but also activate the complement system, thereby enhancing the immune response of subunit vaccines. The results showed that the complex [email protected] could efficiently promote powerful anti-OVA-specific antibody production, enhance CD4+ T- and CD8+ T-cell activation, improve the lymphocyte proliferation efficiency, and increase the secretion of different cytokines. In addition, the abundant amino groups on the surface of [email protected] could effectively activate the complement system to further enhance adaptive immunity. Overall, these results indicated that the triblock copolymer TPCAH as an adjuvant and carrier can effectively improve the ability of innate and adaptive immune responses to resist pathogens, making it a potential candidate for vaccine applications.

Supporting Information

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The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.biomac.9b00887.

  • Related characterizations of mPEG5K-PAGE15-PCL5k (TPCAH) copolymer; part of physical property characterizations, and in vitro and in vivo investigations of the [email protected] complex (PDF)

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Cited By


This article is cited by 1 publications.

  1. Emad I. Wafa, Jennifer H. Wilson-Welder, Richard L. Hornsby, Jarlath E. Nally, Sean M. Geary, Ned B. Bowden, Aliasger K. Salem. Poly(diaminosulfide) Microparticle-Based Vaccine for Delivery of Leptospiral Antigens. Biomacromolecules 2020, 21 (2) , 534-544. https://doi.org/10.1021/acs.biomac.9b01257

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