Conformational stability of SARS-CoV-2 glycoprotein spike variants

Arruda, Hiam R. S.; Lima, Túlio M.; Alvim, Renata G. F.; Victorio, Fernanda B. A.; Abreu, Daniel Paiva Barros de; Marsili, Federico F.; Cruz, Karen D.; Marques, Mayra A.; Sosa‐Acosta, Patricia; Quiñones‐Vega, Mauricio; Guedes, Jéssica de Siqueira; Nogueira, Fábio C. S.; Silva, Jerson L.; Castilho, Leda R.; Oliveira, Guilherme A. P. de

doi:10.1016/j.isci.2022.105696

Cited by 8 publications

(6 citation statements)

References 57 publications

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“…CD exploits the ability of optically active moieties present in proteins to absorb circularly polarized light differentially. The CD signature of M-CoV-S, which is very similar to that of SARS-CoV-2 spike protein, 31 suggests equal percentage of both alpha-helix and beta-sheet structure, with slightly higher content of alpha-helix as modest negative peak can be seen at 222 nm and 208 nm. The similarity in CD signature of SARS-CoV-2 and MERS-spike protein may be attributed to similar geometry and content of the secondary structures in both the spike proteins.…”

Section: In Vitro Expression and Purification Of Recombinant...mentioning

confidence: 74%

“…The 34 nm size seen in case of M-CoV-S further suggests formation of dimer of trimers. 31 Also, a PDI value of 0.25 indicates a uniform distribution of particle sizes of the synthesized M-CoV-S proteins in suspension. Further, the apparent zeta potential of a M-CoV-S protein was determined in the 10 mM PBS (pH 7.5).…”

Section: In Vitro Expression and Purification Of Recombinant...mentioning

confidence: 99%

“…The red shift in case of M-CoV-S may be accounted for the lower number of Trp and higher number of Tyr residues. 31 Nevertheless, a good intensity of emission suggests that the overall M-CoV-S spikes’ structure is folded. 32 …”

Section: In Vitro Expression and Purification Of Recombinant...mentioning

confidence: 99%

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Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Ahuja,

Vishwakarma,

Raj

et al. 2024

Human Vaccines & Immunotherapeutics

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Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal beta-coronavirus that emerged in 2012. The virus is part of the WHO blueprint priority list with a concerning fatality rate of 35%. Scientific efforts are ongoing for the development of vaccines, anti-viral and biotherapeutics, which are majorly directed toward the structural spike protein. However, the ongoing effort is challenging due to conformational instability of the spike protein and the evasion strategy posed by the MERS-CoV. In this study, we have expressed and purified the MERS-CoV pre-fusion spike protein in the Expi293F mammalian expression system. The purified protein was extensively characterized for its biochemical and biophysical properties. Thermal stability analysis showed a melting temperature of 58°C and the protein resisted major structural changes at elevated temperature as revealed by fluorescence spectroscopy and circular dichroism. Immunological assessment of the MERS-CoV spike immunogen in BALB/c mice with AddaVax TM and Imject alum adjuvants showed elicitation of high titer antibody responses but a more balanced Th1/Th2 response with AddaVax TM squalene like adjuvant. Together, our results suggest the formation of higher-order trimeric pre-fusion MERS-CoV spike proteins, which were able to induce robust immune responses. The comprehensive characterization of MERS-CoV spike protein warrants a better understanding of MERS spike protein and future vaccine development efforts.

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Section: In Vitro Expression and Purification Of Recombinant...mentioning

confidence: 74%

Section: In Vitro Expression and Purification Of Recombinant...mentioning

confidence: 99%

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Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Ahuja,

Vishwakarma,

Raj

et al. 2024

Human Vaccines & Immunotherapeutics

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“…Spike glycoprotein of SARS-CoV-2 is one of the major targets of the host immune system. , Receptor-binding domain (RBD) is immunodominant and accounts for major neutralizing activity in the serum of convalescent COVID-19 patients. , However, spike glycoprotein and RBD both suffer from inherently low immunogenicity and poor pharmacokinetics . Appropriate adjuvant or delivery system is an alternative to enhancing the immune effectiveness of the antigens …”

Section: Introductionmentioning

confidence: 99%

Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

Xiao

Wang

Shen

et al. 2023

ACS Appl. Mater. Interfaces

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SARS-CoV-2 is a respiratory virus that causes significant threats to human health. Mucosal immunity provides a first-line defense to prevent the infection of SARS-CoV-2 in the respiratory tract. Because most SARS-CoV-2 vaccines could not stimulate mucosal immunity in the respiratory tract, appropriate mucosal adjuvants or delivery systems are needed for mucosal vaccine development. Mannan, polyarginine, and 2′,3′-cGAMP are three mucosal adjuvants that could stimulate mucosal immunity. In the present study, the three adjuvants were assembled with a receptor-binding domain (RBD) by electrostatic interaction to generate a nanoparticle vaccine (RBD-MP-cG). RBD-MP-cG elicited mucosal IgA and IgG response in bronchoalveolar lavage and nasal lavage by intranasal administration. It induced a robust RBD-specific antibody response, high levels of protective neutralizing antibody, and ACE2-blocking activity in the mouse sera. It stimulated the splenic secretion of high levels of Th1-, Th2-, and Th17-type cytokines. Thus, RBD-MP-cG elicited strong mucosal immunity and systematic immunity by intranasal administration. RBD-MP-cG was expected to act as a safe, effective, and easily produced mucosal nanoparticle vaccine to combat the infection of SARS-CoV-2.

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“…Sequencing of the Severe Acute Respiratory Syndrome CoronaVirus (SARS-CoV)-2 genome enabled the development of mRNA, viral vector, and inactivated vaccines and, more recently, peptide vaccines against the original and newer viral variants. They all aim to generate an immune response against the SARS-CoV-2 spike protein, an envelope glycoprotein that allows the virus to enter target cells by binding to the receptor angiotensin-converting enzyme 2 (ACE 2) [ 2 ]. These vaccines were quickly made available and distributed to people around the world through massive vaccination campaigns.…”

Section: Introductionmentioning

confidence: 99%

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

Talotta¹

2023

Microorganisms

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Background: After the start of the worldwide COVID-19 vaccination campaign, there were increased reports of autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most widely administered COVID-19 vaccines, which could induce autoimmunity in predisposed individuals. Methods: The FASTA sequence of the protein encoded by the BNT-162b2 vaccine served as the key input to the Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC-ligand assays without MHC restriction were searched and analyzed. HLA disease associations were screened on the HLA-SPREAD platform by selecting only positive markers. Results: By 7 May 2023, a total of 5693 epitopes corresponding to 21 viral but also human proteins were found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, and ZFHX2. Importantly, some autoepitopes may be presented by HLA alleles positively associated with various immunological diseases. Conclusions: The protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals through a molecular mimicry mechanism. Genotyping for HLA alleles may help identify individuals at risk. However, further wet-lab studies are needed to confirm this hypothesis.

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Conformational stability of SARS-CoV-2 glycoprotein spike variants

Cited by 8 publications

References 57 publications

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Characterization and immunogenicity assessment of MERS-CoV pre-fusion spike trimeric oligomers as vaccine immunogen

Mucosal SARS-CoV-2 Nanoparticle Vaccine Based on Mucosal Adjuvants and Its Immune Effectiveness by Intranasal Administration

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

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