SARS-CoV-2 Mutations and Their Impact on Diagnostics, Therapeutics and Vaccines

Frontiers in Medicine, Год журнала: 2022, Номер 9

Опубликована: Фев. 22, 2022

With the high rate of COVID-19 infections worldwide, emergence SARS-CoV-2 variants was inevitable. Several mutations have been identified in genome, with spike protein as one mutational hot spots. Specific amino acid substitutions such D614G and N501Y were found to alter transmissibility virulence virus. The WHO has classified fitness-enhancing concern (VOC), interest (VOI) or under monitoring (VUM). VOCs pose an imminent threat they exhibit higher transmissibility, disease severity ability evade vaccine-induced natural immunity. Here we review landscape on structural non-structural proteins their impact diagnostics, therapeutics vaccines. We also look at effectiveness approved vaccines, antibody therapy convalescent plasma currently prevalent VOCs, which are B.1.17, B.1.351, P.1, B.1.617.2 B.1.1.529. further discuss possible factors influencing mutation rates future directions.

Язык: Английский

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Exosome-mediated mRNA delivery in vivo is safe and can be used to induce SARS-CoV-2 immunity

Journal of Biological Chemistry, Год журнала: 2021, Номер 297(5), С. 101266 - 101266

Опубликована: Окт. 1, 2021

Functional delivery of mRNA has high clinical potential. Previous studies established that mRNAs can be delivered to cells in vitro and vivo via RNA-loaded lipid nanoparticles (LNPs). Here we describe an alternative approach using exosomes, the only biologically normal nanovesicle. In contrast LNPs, which elicited pronounced cellular toxicity, exosomes had no adverse effects or at any dose tested. Moreover, mRNA-loaded were characterized by efficient encapsulation (∼90%), content, consistent size, a polydispersity index under 0.2. Using encoding red light-emitting luciferase Antares2, observed superior LNPs delivering functional into human vitro. Injection Antares2 also led strong light emission following injection vitreous fluid eye tissue skeletal muscle mice. Furthermore, show repeated drove sustained expression across six injections spanning least 10 weeks, without evidence signal attenuation site responses. Consistent with these findings, loaded immunogenic forms SARS-CoV-2 Spike Nucleocapsid proteins induced long-lasting humoral responses both. Taken together, results demonstrate used deliver vivo.

Язык: Английский

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Dual spike and nucleocapsid mRNA vaccination confer protection against SARS-CoV-2 Omicron and Delta variants in preclinical models

Science Translational Medicine, Год журнала: 2022, Номер 14(662)

Опубликована: Сен. 14, 2022

Emergence of SARS-CoV-2 variants concern (VOCs), including the highly transmissible Omicron and Delta strains, has posed constant challenges to current COVID-19 vaccines that principally target viral spike protein (S). Here, we report a nucleoside-modified messenger RNA (mRNA) vaccine expresses more conserved nucleoprotein (mRNA-N) show mRNA-N vaccination alone can induce modest control SARS-CoV-2. Critically, combining with clinically proven S-expressing mRNA (mRNA-S+N) induced robust protection against both variants. In hamster models VOC challenge, demonstrated that, compared mRNA-S alone, combination mRNA-S+N not only in lungs but also provided enhanced upper respiratory tract. vivo CD8

Язык: Английский

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Cell surface SARS-CoV-2 nucleocapsid protein modulates innate and adaptive immunity

Science Advances, Год журнала: 2022, Номер 8(31)

Опубликована: Авг. 3, 2022

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody (Ab) and T cell responses. Although considered to be localized in the cytosol, we readily detect N on surface of live cells. released by SARS-CoV-2–infected cells or N-expressing transfected binds neighboring electrostatic high-affinity binding heparan sulfate heparin, but not other sulfated glycosaminoglycans. with high affinity 11 human chemokines, including CXCL12β, whose chemotaxis leukocytes is inhibited from SARS-CoV-2, SARS-CoV-1, MERS-CoV. Anti-N Abs bound activate Fc receptor–expressing Our findings indicate that manipulates innate immunity sequestering chemokines can targeted Fc-expressing immune This, combination its conserved antigenicity among CoVs, advances candidacy for vaccines induce cross-reactive B variants novel zoonotic strains.

Язык: Английский

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The Remarkable Evolutionary Plasticity of Coronaviruses by Mutation and Recombination: Insights for the COVID-19 Pandemic and the Future Evolutionary Paths of SARS-CoV-2

Viruses, Год журнала: 2022, Номер 14(1), С. 78 - 78

Опубликована: Янв. 2, 2022

Coronaviruses (CoVs) constitute a large and diverse subfamily of positive-sense single-stranded RNA viruses. They are found in many mammals birds have great importance for the health humans farm animals. The current SARS-CoV-2 pandemic, as well previous epidemics that were zoonotic origin, highlights studying evolution entire CoV order to understand how novel strains emerge which molecular processes affect their adaptation, transmissibility, host/tissue tropism, patho non-homologous genicity. In this review, we focus on studies over last two years reveal impact point mutations, insertions/deletions, intratypic/intertypic homologous recombination events CoVs. We discuss whether next generations vaccines should be directed against other proteins addition or instead spike. Based observed patterns subfamily, five scenarios future evolutionary path COVID-19 pandemic. Finally, within context, recently emerged Omicron (B.1.1.529) VoC.

Язык: Английский

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An Update on Anti-COVID-19 Vaccines and the Challenges to Protect Against New SARS-CoV-2 Variants

Pathogens, Год журнала: 2025, Номер 14(1), С. 23 - 23

Опубликована: Янв. 1, 2025

The COVID-19 pandemic has posed a significant threat to global health systems, with extensive impacts across many sectors of society. been responsible for millions deaths worldwide since its first identification in late 2019. Several actions have taken prevent the disease, including unprecedented fast development and vaccination campaigns, which were pivotal reducing symptoms deaths. Given impact pandemic, continuous changes virus, present vaccine technologies, this review analyzes how, so far, we met challenge by emergence new variants discusses how next-generation pan-coronavirus vaccines, enhanced longevity breadth immune responses, may be tackled alternative administration routes antigen delivery platforms. By addressing these critical aspects, aims contribute ongoing efforts achieve long-term control COVID-19, stimulating discussion work on vaccines capable facing future waves infection.

Язык: Английский

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Comparison of antibody and T cell responses elicited by BBIBP-CorV (Sinopharm) and BNT162b2 (Pfizer-BioNTech) vaccines against SARS-CoV-2 in healthy adult humans

GeroScience, Год журнала: 2021, Номер 43(5), С. 2321 - 2331

Опубликована: Окт. 1, 2021

Abstract In the present study, humoral and T cell-mediated immune responses elicited by BBIBP-CorV (inactivated virus) BNT162b2 (mRNA-based) vaccines against SARS-CoV-2 virus were compared. Convalescent volunteers also investigated to evaluate adaptive immunity induced live virus. Although both antibody- responses, our analysis revealed significant quantitative qualitative differences between two types of challenges. The vaccine antireceptor-binding domain (RBD) IgG, as well anti-spike protein (S) IgG IgA antibodies in healthy individuals, levels which much lower than after vaccination but still higher convalescent patients. cumulative IFNγ-positive cell response, however, was only twofold participants injected with compared those who primed boosted vaccine. Moreover, inactivated response that targets not S nucleocapsid (N) membrane (M) proteins, whereas mRNA able elicit a narrower epitopes only. Thus, pattern BBIBP-CorV-induced virus-naive similar anti-SARS-CoV-2 observed Based on these data, we can conclude is immunologically effective. However, duration integrated, antibody, cell-mediated, needs further investigation.

Язык: Английский

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T cell immunity to SARS-CoV-2

Seminars in Immunology, Год журнала: 2021, Номер 55, С. 101505 - 101505

Опубликована: Июнь 1, 2021

Exceptional efforts have been undertaken to shed light into the biology of adaptive immune responses SARS-CoV-2. T cells occupy a central role in immunity mediate helper functions different arms system and are fundamental protection, control, clearance most viral infections. Even though many questions remain unsolved, there is growing literature linking specific cell characteristics differential COVID-19 severity vaccine outcome. In this review, we summarize our current understanding CD4+ CD8+ acute convalescent COVID-19. Further, discuss coupled pre-existing vaccines highlight need look beyond blood fully understand how function tissue space.

Язык: Английский

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Improved control of SARS-CoV-2 by treatment with a nucleocapsid-specific monoclonal antibody

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(23)

Опубликована: Окт. 11, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and also only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine then transferred sera from these into naive mice, followed by challenge show that received or mAb exhibited enhanced control of Nucleocapsid-specific elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) infected cells. To our knowledge, findings provide demonstration literature specific nucleocapsid clearance, providing rationale clinical evaluation therapies treat COVID-19.

Язык: Английский

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Synthetic multiantigen MVA vaccine COH04S1 protects against SARS-CoV-2 in Syrian hamsters and non-human primates

npj Vaccines, Год журнала: 2022, Номер 7(1)

Опубликована: Янв. 21, 2022

Second-generation COVID-19 vaccines could contribute to establish protective immunity against SARS-CoV-2 and its emerging variants. We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara-based vaccine that co-expresses spike nucleocapsid antigens. Here, we report COH04S1 efficacy in animal models. demonstrate intramuscular or intranasal vaccination of Syrian hamsters with induces robust Th1-biased antigen-specific humoral cross-neutralizing antibodies (NAb) protects weight loss, lower respiratory tract infection, lung injury following challenge. Moreover, single-dose two-dose non-human primates binding antibodies, NAb, T cells, both upper infection intranasal/intratracheal challenge, triggers potent post-challenge anamnestic antiviral responses. These results COH04S1-mediated protection models through different routes dose regimens, complementing ongoing investigation this clinical trials.

Язык: Английский

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