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A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone

  1. Author:
    Zhang, Baoshan
    Chao, Cara W
    Tsybovsky,Yaroslav
    Abiona, Olubukola M
    Hutchinson, Geoffrey B
    Moliva, Juan I
    Olia, Adam S
    Pegu, Amarendra
    Phung, Emily
    Stewart-Jones, Guillaume B E
    Verardi, Raffaello
    Wang, Lingshu
    Wang, Shuishu
    Werner, Anne
    Yang, Eun Sung
    Yap, Christina
    Zhou, Tongqing
    Mascola, John R
    Sullivan, Nancy J
    Graham, Barney S
    Corbett, Kizzmekia S
    Kwong, Peter D

  2. Author Address

    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA., Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Institute for Biomedical Sciences, George Washington University, Washington, DC, USA., Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. pdkwong@nih.gov.,
    1. Year: 2020
    2. Date: Oct 23
    3. Epub Date: 2020 10 23
  2. Journal: Scientific reports
    1. 10
    2. 1
    3. Pages: 18149
  4. Type of Article: Article
  5. Article Number: 18149
  6. ISSN: 2045-2322
  1. Abstract:

    Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer-stabilized in the prefusion conformation and fused with SpyCatcher-could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 181;g of SARS-CoV-2 spike-LuS nanoparticle elicited 160;similar neutralizing responses as 2.0 181;g of spike, which was?~?25-fold higher 160;on a 160;weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41598-020-74949-2
  3. PMID: 33097791
  4. View record in Web of Science®
  5. WOS: 000586485700007
  6. PII : 10.1038/s41598-020-74949-2

Library Notes

  1. Fiscal Year: FY2020-2021
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