A COVID-19 vaccine candidate composed of the SARS-CoV-2 RBD dimer and <i>Neisseria meningitidis</i> outer membrane vesicles†‡

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Abstract

SARS-CoV-2 infection is mediated by the interaction of the spike glycoprotein trimer via its receptor-binding domain (RBD) with the host's cellular receptor. Vaccines seek to block this interaction by eliciting neutralizing antibodies, most of which are directed toward the RBD. Many protein subunit vaccines require powerful adjuvants to generate a potent antibody response. Here, we report on the use of a SARS-CoV-2 dimeric recombinant RBD combined with Neisseria meningitidis outer membrane vesicles (OMVs), adsorbed on alum, as a promising COVID-19 vaccine candidate. This formulation induces a potent and neutralizing immune response in laboratory animals, which is higher than that of the dimeric RBD alone adsorbed on alum. Sera of people vaccinated with this vaccine candidate, named Soberana01, show a high inhibition level of the RBD-ACE2 interaction using RBD mutants corresponding to SARS-CoV-2 variants of concern and wild-type expressed using the phage display technology. To our knowledge, this is the first time that the immunostimulation effect of N. meningitidis OMVs is evaluated in vaccine candidates against SARS-CoV-2.

Abstract

Soberana01 is composed of the SARS-CoV-2 dimeric RBD and Neisseria meningitidis outer membrane vesicles (OMVs) adsorbed on alum. This vaccine induces a potent neutralizing immune response and shows potential against SARS-CoV-2 variants of concern.

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Most cited references 36

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Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C Walls, Young-Jun Park, M. Alejandra Tortorici … (2020)

Summary The emergence of SARS-CoV-2 has resulted in >90,000 infections and >3,000 deaths. Coronavirus spike (S) glycoproteins promote entry into cells and are the main target of antibodies. We show that SARS-CoV-2 S uses ACE2 to enter cells and that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, correlating with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and SARS-related CoVs. We determined cryo-EM structures of the SARS-CoV-2 S ectodomain trimer, providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal antibodies potently inhibited SARS-CoV-2 S mediated entry into cells, indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.

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Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

Jun Lan, Jiwan Ge, Jinfang Yu … (2020)

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

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Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus

Yushun Wan, Jian Shang, Rachel Graham … (2020)

The recent emergence of Wuhan coronavirus (2019-nCoV) puts the world on alert. 2019-nCoV is reminiscent of the SARS-CoV outbreak in 2002 to 2003. Our decade-long structural studies on the receptor recognition by SARS-CoV have identified key interactions between SARS-CoV spike protein and its host receptor angiotensin-converting enzyme 2 (ACE2), which regulate both the cross-species and human-to-human transmissions of SARS-CoV. One of the goals of SARS-CoV research was to build an atomic-level iterative framework of virus-receptor interactions to facilitate epidemic surveillance, predict species-specific receptor usage, and identify potential animal hosts and animal models of viruses. Based on the sequence of 2019-nCoV spike protein, we apply this predictive framework to provide novel insights into the receptor usage and likely host range of 2019-nCoV. This study provides a robust test of this reiterative framework, providing the basic, translational, and public health research communities with predictive insights that may help study and battle this novel 2019-nCoV.

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Author and article information

Journal

Journal ID (nlm-ta): RSC Chem Biol

Journal ID (iso-abbrev): RSC Chem Biol

Journal ID (publisher-id): CB

Journal ID (coden): RCBSAO

Title: RSC Chemical Biology

Publisher: RSC

ISSN (Electronic): 2633-0679

Publication date (Electronic, pub): 8 December 2021

Publication date (Electronic, collection): 9 February 2022

Publication date PMC-release: 8 December 2021

Volume: 3

Issue: 2

Pages: 242-249

Affiliations

[a] Finlay Vaccine Institute 200 and 21 Street Havana 11600 Cuba yvbalbin@ 123456finlay.edu.cu dagarcia@ 123456finlay.edu.cu vicente.verez@ 123456finlay.edu.cu

[b] Center of Molecular Immunology P.O. Box 16040 216 St. Havana Cuba

[c] National Toxicology Center Havana 11500 Cuba

[d] National Civil Defense Research Laboratory Mayabeque 32700 Cuba

[e] Center for Genetic Engineering and Biotechnology Ave 31 e/158 y 190 Havana 10600 Cuba

[f] Institute of Cybernetics, Mathematics and Physics Havana 10400 Cuba

[g] Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands and Institute of Biomolecular Chemistry, National Research Council (CNR) Pozzuoli Napoli Italy

[h] Centre de Biophysique Moléculaire, CNRS UPR 4301, rue Charles Sadron F-45071 Orléans Cedex 2 France

[i] Shanghai Fenglin Glycodrug Promotion Center Shanghai 200032 China

[j] Chengdu Olisynn Biotech. Co. Ltd., and State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University Chengdu 610041 People's Republic of China

[k] Laboratory of Synthetic and Biomolecular Chemistry, Faculty of Chemistry, University of Havana, Zapata y G Havana 10400 Cuba dgr@ 123456fq.uh.cu