Modularized viromimetic polymer nanoparticle vaccines (VPNVaxs) to elicit durable and effective humoral immune responses

Zichao Huang; Xinyu Zhuang; Liping Liu; Jiayu Zhao; Sheng Ma; Xinghui Si; Zhenyi Zhu; Fan Wu; Ningyi Jin; Mingyao Tian; Wantong Song; Xuesi Chen

doi:10.1093/nsr/nwad310

Modularized viromimetic polymer nanoparticle vaccines (VPNVaxs) to elicit durable and effective humoral immune responses

Natl Sci Rev. 2023 Dec 7;11(3):nwad310. doi: 10.1093/nsr/nwad310. eCollection 2024 Mar.

Authors

Zichao Huang^{1

2}, Xinyu Zhuang³, Liping Liu^{1

2}, Jiayu Zhao^{1

2}, Sheng Ma^{1

4}, Xinghui Si^{1

4}, Zhenyi Zhu^{1

2}, Fan Wu⁵, Ningyi Jin³, Mingyao Tian³, Wantong Song^{1

2

4}, Xuesi Chen^{1

2

4}

Affiliations

¹ Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
² School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China.
³ Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China.
⁴ Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China.
⁵ State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

Abstract

Virus-like particle (VLP) vaccines had shown great potential during the COVID-19 pandemic, and was thought to be the next generation of antiviral vaccine technology due to viromimetic structures. However, the time-consuming and complicated processes in establishing a current recombinant-protein-based VLP vaccine has limited its quick launch to the out-bursting pandemic. To simplify and optimize VLP vaccine design, we herein report a kind of viromimetic polymer nanoparticle vaccine (VPNVax), with subunit receptor-binding domain (RBD) proteins conjugated to the surface of polyethylene glycol-b-polylactic acid (PEG-b-PLA) nanoparticles for vaccination against SARS-CoV-2. The preparation of VPNVax based on synthetic polymer particle and chemical post-conjugation makes it possible to rapidly replace the antigens and construct matched vaccines at the emergence of different viruses. Using this modular preparation system, we identified that VPNVax with surface protein coverage of 20%-25% had the best immunostimulatory activity, which could keep high levels of specific antibody titers over 5 months and induce virus neutralizing activity when combined with an aluminum adjuvant. Moreover, the polymer nano-vectors could be armed with more immune-adjuvant functions by loading immunostimulant agents or chemical chirality design. This VPNVax platform provides a novel kind of rapidly producing and efficient vaccine against different variants of SARS-CoV-2 as well as other viral pandemics.

Keywords: SARS-CoV-2; nanomaterials; polymer; vaccine.