Characterization of cytotoxic T‐lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD‐integrin‐binding motif

“…Thus, mAbs 1A9 will be useful for studying the kinetics of SARS-CoV-2 replication in vitro and development of diagnostic assays for COVID-19. It is noteworthy that cytotoxic T-lymphocyte (CTL) epitopes also reside at residues 884-891 and 1116-1123 within the S2 subunit of SARS-CoV-1 [30]. Interestingly, the latter CTL epitope overlaps with the epitope recognised by mAb 1A9 [21].…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

et al. 2020

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Background: A novel coronavirus, SARS-CoV-2, which emerged at the end of 2019 and causes COVID-19, has resulted in worldwide human infections. While genetically distinct, SARS-CoV-1, the aetiological agent responsible for an outbreak of severe acute respiratory syndrome (SARS) in 2002-2003, utilises the same host cell receptor as SARS-CoV-2 for entry: angiotensin-converting enzyme 2 (ACE2). Parts of the SARS-CoV-1 spike glycoprotein (S protein), which interacts with ACE2, appear conserved in SARS-CoV-2. Aim: The cross-reactivity with SARS-CoV-2 of monoclonal antibodies (mAbs) previously generated against the S protein of SARS-CoV-1 was assessed. Methods: The SARS-CoV-2 S protein sequence was aligned to those of SARS-CoV-1, Middle East respiratory syndrome (MERS) and common-cold coronaviruses. Abilities of mAbs generated against SARS-CoV-1 S protein to bind SARS-CoV-2 or its S protein were tested with SARS-CoV-2 infected cells as well as cells expressing either the full length protein or a fragment of its S2 subunit. Quantitative ELISA was also performed to compare binding of mAbs to recombinant S protein. Results: An immunogenic domain in the S2 subunit of SARS-CoV-1 S protein is highly conserved in SARS-CoV-2 but not in MERS and human common-cold coronaviruses. Four murine mAbs raised against this immunogenic fragment could recognise SARS-CoV-2 S protein expressed in mammalian cell lines. In particular, mAb 1A9 was demonstrated to detect S protein in SARS-CoV-2infected cells and is suitable for use in a sandwich ELISA format. Conclusion: The cross-reactive mAbs may serve as useful tools for SARS-CoV-2 research and for the development of diagnostic assays for COVID-19.

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“…This S2 function of membrane fusion was inferred early because many antibodies targeting S2 of coronavirus S proteins were almost always associated with disrupted membrane fusion [ 17 ]. Vaccine targeting segments 884–891 and 1116–1123 in S2 were highly effective in inducing humoral and cell-mediated immune responses [ 65 ]. These segments belong to the central helix between HR1 and HR2.…”

Section: The S2 Domainmentioning

confidence: 99%

Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design

Xia

2021

Viruses

279

239

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The spike protein in SARS-CoV-2 (SARS-2-S) interacts with the human ACE2 receptor to gain entry into a cell to initiate infection. Both Pfizer/BioNTech’s BNT162b2 and Moderna’s mRNA-1273 vaccine candidates are based on stabilized mRNA encoding prefusion SARS-2-S that can be produced after the mRNA is delivered into the human cell and translated. SARS-2-S is cleaved into S1 and S2 subunits, with S1 serving the function of receptor-binding and S2 serving the function of membrane fusion. Here, I dissect in detail the various domains of SARS-2-S and their functions discovered through a variety of different experimental and theoretical approaches to build a foundation for a comprehensive mechanistic understanding of how SARS-2-S works to achieve its function of mediating cell entry and subsequent cell-to-cell transmission. The integration of structure and function of SARS-2-S in this review should enhance our understanding of the dynamic processes involving receptor binding, multiple cleavage events, membrane fusion, viral entry, as well as the emergence of new viral variants. I highlighted the relevance of structural domains and dynamics to vaccine development, and discussed reasons for the spike protein to be frequently featured in the conspiracy theory claiming that SARS-CoV-2 is artificially created.

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Characterization of cytotoxic T‐lymphocyte epitopes and immune responses to SARS coronavirus spike DNA vaccine expressing the RGD‐integrin‐binding motif

Cited by 15 publications

References 44 publications

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV cross-react with the newly-emerged SARS-CoV-2

Monoclonal antibodies for the S2 subunit of spike of SARS-CoV-1 cross-react with the newly-emerged SARS-CoV-2

Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design

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