Mutations in SARS-CoV-2: Insights on structure, variants, vaccines, and biomedical interventions

Biomedicine & Pharmacotherapy, Год журнала: 2022, Номер 157, С. 113977 - 113977

Опубликована: Ноя. 7, 2022

COVID-19 is a worldwide pandemic caused by SARS-coronavirus-2 (SARS-CoV-2). Less than year after the emergence of Covid-19 pandemic, many vaccines have arrived on market with innovative technologies in field vaccinology. Based use messenger RNA (mRNA) encoding Spike SARS-Cov-2 protein or recombinant adenovirus vectors enabling gene to be introduced into our cells, these strategies make it possible envisage vaccination new light tools that are more scalable vaccine used so far. Faced appearance variants, which will gradually take precedence over strain at origin allow much faster update fight against some may escape neutralization antibodies. However, only policy based rapid and massive population but requiring supply sufficient doses could combat variants. Indeed, greater number infected individuals, virus multiplies, an increased risk variants viruses. This review discuss SARS-CoV-2 pathophysiology evolution approaches altered transmission platforms emphasize different mutations how they influence characteristics. Also, this article summarizes common implication genetic variety biomedical arbitrations.

Язык: Английский

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Challenges in the Vaccination of the Elderly and Strategies for Improvement

Pathophysiology, Год журнала: 2023, Номер 30(2), С. 155 - 173

Опубликована: Апрель 22, 2023

In recent years, the elderly has become a rapidly growing proportion of world's population as life expectancy is extending. Immunosenescence and inflammaging contribute to increased risk chronic non-communicable acute infectious diseases. Frailty highly prevalent in associated with an impaired immune response, higher propensity infection, lower response vaccines. Additionally, presence uncontrolled comorbid diseases also contributes sarcopenia frailty. Vaccine-preventable that threaten include influenza, pneumococcal herpes zoster, COVID-19, which significant disability-adjusted years lost. Previous studies had shown conventional vaccines only yielded suboptimal protection wanes shorter time. This article reviews published papers on several vaccination strategies were developed for solve these problems: more immunogenic vaccine formulations using larger doses antigen, stronger adjuvants, recombinant subunit or protein conjugated vaccines, newly mRNA giving booster shots, exploring alternative routes administration. Included are publications senolytic medications under investigation boost system elderly. With all those regard, currently recommended presented.

Язык: Английский

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Molecular insights into the adaptive evolution of SARS-CoV-2 spike protein

Journal of Infection, Год журнала: 2024, Номер 88(3), С. 106121 - 106121

Опубликована: Фев. 16, 2024

The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has substantially damaged global economy and human health. spike (S) protein of coronaviruses plays a pivotal role in viral entry binding to host cell receptors. Additionally, it acts as primary target for neutralizing antibodies those infected is central focus currently utilized or researched vaccines. During virus's adaptation host, S SARS-CoV-2 undergone significant evolution. As pandemic unfolded, new mutations have arisen vanished, giving rise distinctive amino acid profiles within variant concern strains SARS-CoV-2. Notably, many these changes been positively selected, leading substantial alterations characteristics, such heightened transmissibility immune evasion capabilities. This review aims provide an overview our current understanding structural implications associated with key These research findings shed light on intricate dynamic nature evolution, underscoring importance continuous monitoring analysis genomes. Through molecular-level investigations, we can attain deeper insights into adaptive offering valuable guidance designing vaccines developing antiviral drugs combat ever-evolving threats.

Язык: Английский

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What makes SARS‐CoV‐2 unique? Focusing on the spike protein

Cell Biology International, Год журнала: 2024, Номер 48(4), С. 404 - 430

Опубликована: Янв. 23, 2024

Abstract Severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) seriously threatens public health and safety. Genetic variants determine the expression of SARS‐CoV‐2 structural proteins, which are associated with enhanced transmissibility, virulence, immune escape. Vaccination is encouraged as a intervention, different types vaccines used worldwide. However, new continue to emerge, especially Omicron complex, neutralizing antibody responses diminished significantly. In this review, we outlined uniqueness from three perspectives. First, described detailed structure spike (S) protein, highly susceptible mutations contributes distinct infection cycle virus. Second, systematically summarized immunoglobulin G epitopes highlighted central role nonconserved regions S protein in adaptive Third, provided an overview targeting discussed impact on vaccine effectiveness. The characterization identification genomic organization will help elucidate its mechanisms viral mutation provide basis for selection optimal treatments. leaps advancements regarding improved diagnosis, targeted therapeutic remedies sound evidence showing that scientific understanding, research, technology evolved at pace pandemic.

Язык: Английский

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Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 12, 2024

Abstract The 2002 SARS outbreak, the 2019 emergence of COVID-19, and continuing evolution immune-evading SARS-CoV-2 variants together highlight need for a broadly protective vaccine against ACE2-utilizing sarbecoviruses. While updated variant-matched formulations are step in right direction, protection needs to extend beyond its include SARS-like viruses. Here, we introduce bivalent trivalent using our spike protein nanoparticle platform that completely protect female hamsters BA.5 XBB.1 challenges with no detectable virus lungs. cocktails elicit highly neutralizing responses all tested Omicron bat sarbecoviruses SHC014 WIV1. Finally, 614D/SHC014/XBB formulation protects human ACE2-transgenic WIV1 Collectively, these results illustrate protein-nanoparticle cocktail can provide broad SARS-CoV-2-like SARS-CoV-1-like

Язык: Английский

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Enhanced stability and efficacy of a lyophilized mRNA SARS-CoV-2 vaccine incorporating novel Ionizable lipids after one year storage at 25ºC

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

mRNA vaccines have shown great efficacy against SARS-CoV-2, yet challenges remain in optimizing vaccine components to achieve enhanced immune response and stability. In this study, we developed CPVax-CoV, a new lyophilized that features novel thiolactone-based ionizable lipids newly designed untranslated regions (UTRs) for expression. Incorporation of these optimized into our candidate CPVax-CoV significantly improved responses mice compared commercially available vaccines. Moreover, has proven be thermostable, maintaining its biological activity up one year at 4°C 25°C after lyophilization, overcoming the cold-chain limitations current This demonstrates protective ancestral SARS-CoV-2 Omicron XBB variant, offering scalable solution global distribution pandemic preparedness. These findings underscore potential platform future next-generation development.

Язык: Английский

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Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Adults with Underlying Medical Conditions: Systematic Literature Review and Pairwise Meta-Analysis Using GRADE

Advances in Therapy, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b2 in patients with at least one underlying medical condition high risk for severe COVID-19. MEDLINE, Embase, Cochrane databases were searched relevant articles from January 1, 2019 to February 9, 2024. Studies reporting data two doses vaccination adults conditions developing COVID-19 according US Centers Disease Control Prevention included. Outcomes interest SARS-CoV-2 infection (overall, symptomatic, severe), hospitalization due COVID-19, death Risk ratios (RRs) calculated random effects models. Subgroup analyses by specific conditions, number vaccinations, age, variant conducted. Heterogeneity between studies was estimated chi-square testing. The certainty evidence assessed using Grading Recommendations, Assessments, Development, Evaluations framework. Sixty-five observational capturing original/ancestral-containing primary series Omicron-containing bivalent original-BA4-5 vaccinations included meta-analysis. associated significantly lower (RR, 0.85 [95% CI, 0.79–0.92]; I2 = 92.5%), symptomatic 0.75 0.65–0.86]; 62.3%), 0.83 0.78–0.89]; 38.0%), 0.88 0.82–0.94]; 38.7%), 0.84 0.76–0.93]; 1.3%) than BNT162b2. Findings generally consistent across subgroups. Evidence low or very because sufficiently powered randomized controlled trials are impractical this heterogeneous population. Meta-analysis 65 showed that a COVID-19-related

Язык: Английский

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Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Май 23, 2024

Abstract The rapid development and deployment of vaccines following the emergence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions lives. Despite their immense success, there remains a need for next-generation vaccination approaches SARS-CoV-2 future emerging coronaviruses other viruses. Here we utilized Newcastle Disease virus (NDV) vectored vaccine expressing ancestral spike protein in pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters K18 mice against Delta Omicron variants concern. Additionally, intranasal induced robust, durable protection that was extended 6 months post-vaccination. Overall, our data provide evidence NDV-vectored represent viable mucosal approach.

Язык: Английский

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Vaccine process technology—A decade of progress

Biotechnology and Bioengineering, Год журнала: 2024, Номер 121(9), С. 2604 - 2635

Опубликована: Май 6, 2024

In the past decade, new approaches to discovery and development of vaccines have transformed field. Advances during COVID-19 pandemic allowed production billions vaccine doses per year using novel platforms such as messenger RNA viral vectors. Improvements in analytical toolbox, equipment, bioprocess technology made it possible achieve both unprecedented speed scale manufacturing. Macromolecular structure-function characterization technologies, combined with improved modeling data analysis, enable quantitative evaluation formulations at single-particle resolution guided design drug substances products. These advances play a major role precise assessment critical quality attributes delivered by newer platforms. Innovations label-free immunoassay technologies aid antigenic sites robust vitro potency assays. methods, along molecular techniques next-generation sequencing, will accelerate release all Process for real-time monitoring optimization process steps implementation quality-by-design principles faster next field continue advance, bringing together improve human health.

Язык: Английский

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Self-assembled ferritin-based nanoparticles elicit a robust broad-spectrum protective immune response against SARS-CoV-2 variants

International Journal of Biological Macromolecules, Год журнала: 2024, Номер 264, С. 130820 - 130820

Опубликована: Март 12, 2024

Язык: Английский

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