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SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung

Author

Listed:
  • Nanda Kishore Routhu

    (Emory University
    Emory University)

  • Narayanaiah Cheedarla

    (Emory University
    Emory University)

  • Venkata Satish Bollimpelli

    (Emory University
    Emory University)

  • Sailaja Gangadhara

    (Emory University
    Emory University)

  • Venkata Viswanadh Edara

    (Emory University
    Emory University School of Medicine)

  • Lilin Lai

    (Emory University
    Emory University School of Medicine)

  • Anusmita Sahoo

    (Emory University
    Emory University)

  • Ayalnesh Shiferaw

    (Emory University
    Emory University)

  • Tiffany M. Styles

    (Emory University
    Emory University)

  • Katharine Floyd

    (Emory University
    Emory University School of Medicine)

  • Stephanie Fischinger

    (MIT and Harvard)

  • Caroline Atyeo

    (MIT and Harvard)

  • Sally A. Shin

    (MIT and Harvard)

  • Sanjeev Gumber

    (Emory University)

  • Shannon Kirejczyk

    (Emory University)

  • Kenneth H. Dinnon

    (University of North Carolina)

  • Pei-Yong Shi

    (The University of Texas Medical Branch)

  • Vineet D. Menachery

    (The University of Texas Medical Branch)

  • Mark Tomai

    (3M Corporate Research Materials Laboratory)

  • Christopher B. Fox

    (Infectious Disease Research Institute)

  • Galit Alter

    (MIT and Harvard)

  • Thomas H. Vanderford

    (Emory University)

  • Lisa Gralinski

    (University of North Carolina)

  • Mehul S. Suthar

    (Emory University
    Emory University
    Emory University School of Medicine)

  • Rama Rao Amara

    (Emory University
    Emory University)

Abstract

There is a great need for the development of vaccines that induce potent and long-lasting protective immunity against SARS-CoV-2. Multimeric display of the antigen combined with potent adjuvant can enhance the potency and longevity of the antibody response. The receptor binding domain (RBD) of the spike protein is a primary target of neutralizing antibodies. Here, we developed a trimeric form of the RBD and show that it induces a potent neutralizing antibody response against live virus with diverse effector functions and provides protection against SARS-CoV-2 challenge in mice and rhesus macaques. The trimeric form induces higher neutralizing antibody titer compared to monomer with as low as 1μg antigen dose. In mice, adjuvanting the protein with a TLR7/8 agonist formulation alum-3M-052 induces 100-fold higher neutralizing antibody titer and superior protection from infection compared to alum. SARS-CoV-2 infection causes significant loss of innate cells and pathology in the lung, and vaccination protects from changes in innate cells and lung pathology. These results demonstrate RBD trimer protein as a suitable candidate for vaccine against SARS-CoV-2.

Suggested Citation

  • Nanda Kishore Routhu & Narayanaiah Cheedarla & Venkata Satish Bollimpelli & Sailaja Gangadhara & Venkata Viswanadh Edara & Lilin Lai & Anusmita Sahoo & Ayalnesh Shiferaw & Tiffany M. Styles & Katharin, 2021. "SARS-CoV-2 RBD trimer protein adjuvanted with Alum-3M-052 protects from SARS-CoV-2 infection and immune pathology in the lung," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23942-y
    DOI: 10.1038/s41467-021-23942-y
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    Cited by:

    1. Jiao Qu & Fa Yang & Tao Zhu & Yingshuo Wang & Wen Fang & Yan Ding & Xue Zhao & Xianjia Qi & Qiangmin Xie & Ming Chen & Qiang Xu & Yicheng Xie & Yang Sun & Dijun Chen, 2022. "A reference single-cell regulomic and transcriptomic map of cynomolgus monkeys," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Dapeng Li & David R. Martinez & Alexandra Schäfer & Haiyan Chen & Maggie Barr & Laura L. Sutherland & Esther Lee & Robert Parks & Dieter Mielke & Whitney Edwards & Amanda Newman & Kevin W. Bock & Mahn, 2022. "Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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