Vaccination against SARS-CoV-2 provides low-level cross-protection against common cold coronaviruses in mouse and non-human primate animal models

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

ABSTRACT The common cold coronaviruses are a source of ongoing morbidity and mortality particularly among elderly immunocompromised individuals. While cross-reactive immune responses against multiple have been described following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection vaccination, it remains unclear if these confer any degree cross-protection the coronaviruses. A recombinant fowl adenovirus vaccine expressing SARS-CoV-2 spike protein (FAdV-9-S19) was generated, protection from challenge shown in K18-hACE2 mice. Vaccinated mice were also challenged with human (HCoV)-OC43 HCoV-NL63 by intranasal route, viral shedding lung burden reduced groups compared to unvaccinated animals. Histopathological analysis tissues revealed significantly less inflammation lower pathology scores that received FAdV-9-S19 . Because no mouse model for HCoV-229E exists, we vaccinated cynomolgus macaques evaluate HCoV-229E. Animals monitored clinical signs disease shedding. Infectious virus detected both throughout course infection; however, animals showed at time points after infection. indicated more moderate Therefore, vaccination provided model. Our study demonstrates can provide low-level beta- alphacoronaviruses. These findings important design future pan-coronavirus vaccines. IMPORTANCE individuals, is currently available. Cross-reactive vaccination; what they We demonstrate humoral cell-mediated cross-protection, resulting load OC43 NL63 models. Additionally, present novel non-human primate (NHP) 229E, demonstrating mimics observed humans serve as studies, observed. This significant suggests current vaccines could other part strategy

Language: Английский

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Host Membranes as Drivers of Virus Evolution

Viruses, Journal Year: 2023, Volume and Issue: 15(9), P. 1854 - 1854

Published: Aug. 31, 2023

The molecular mechanisms controlling the adaptation of viruses to host cells are generally poorly documented. An essential issue resolve is whether membranes, and especially lipid rafts, which usually considered passive gateways for many enveloped viruses, also encode informational guidelines that could determine virus evolution. Due their enrichment in gangliosides confer an electronegative surface potential, rafts impose a first control level favoring selection with enhanced cationic areas, as illustrated by SARS-CoV-2 variants. Ganglioside clusters attract viral particles dynamic electrostatic funnel, more population winning race. However, forces account only small part energy raft-virus interaction, depends mainly on ability form network hydrogen bonds raft gangliosides. This fine tuning virus-ganglioside interactions, stabilize membrane, generates second pressure driven typical induced-fit mechanism. Gangliosides play active role this process, wrapping around spikes through quicksand-like Viruses thus endless race access they bound evolve perpetually, combining speed (electrostatic potential) precision (fine amino acids) under selective immune system. Deciphering membrane evolution may open new avenues design innovative antivirals.

Language: Английский

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SARS-CoV-2 mRNA Vaccines Induce Cross-Reactive Antibodies to NL63 Coronavirus but Do Not Boost Pre-Existing Immunity Anti-NL63 Antibody Responses

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 268 - 268

Published: March 4, 2025

Background/Objectives: mRNA vaccines have demonstrated strong immunogenicity and efficacy against SARS-CoV-2. However, the extent of antibody cross-reactivity human seasonal coronaviruses, such as NL63, remains unclear. Furthermore, it is unknown whether pre-existing responses NL63 might influence outcome SARS-CoV-2 vaccination. Methods: We used a flow cytometry-based serological assay an in vitro neutralization to analyze sera from mRNA-vaccinated mice plasma samples vaccinated cohort. Results: found that Moderna mRNA-1273 vaccine can generate cross-reactive antibodies NL63. Importantly, vaccination did not boost anti-NL63 humans, levels affect response induced by Conclusions: These findings suggest while induce immunity this coronavirus does appear significantly impact immunogenicity. contribute our understanding complex interplay between coronaviruses immune generated vaccines.

Language: Английский

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Enhanced Assessment of Cross-Reactive Antigenic Determinants within the Spike Protein

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8180 - 8180

Published: July 26, 2024

Despite successful vaccination efforts, the emergence of new SARS-CoV-2 variants poses ongoing challenges to control COVID-19. Understanding humoral responses regarding infections and their impact is crucial for developing future vaccines that are effective worldwide. Here, we identified 41 immunodominant linear B-cell epitopes in its spike glycoprotein with an SPOT synthesis peptide array probed a pool serum from hospitalized COVID-19 patients. The bioinformatics showed restricted set unique compared other coronavirus family members. Potential crosstalk was also detected Dengue virus (DENV), which confirmed by screening individuals infected DENV before pandemic commercial ELISA anti-SARS-CoV-2 antibodies. A high-resolution evaluation antibody reactivity against peptides representing protein ten sequences NTD, RBD, S2 domains. Functionally, antibody-dependent enhancement (ADE) monocytes observed vitro pre-pandemic Dengue-positive sera. significant increase viral load measured controls, no detectable neutralization or considerable cell death, suggesting role entry. Cross-reactivity proteins This study highlights importance identifying specific generated during response pathogenic infection understand potential interplay previous on diseases vaccinations immunodiagnostics.

Language: Английский

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Ethno‐demographic disparities in humoral responses to the COVID‐19 vaccine among healthcare workers

Journal of Medical Virology, Journal Year: 2023, Volume and Issue: 95(9)

Published: Sept. 1, 2023

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in significant decline morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes humoral immune response against SARS-CoV-2 healthcare workers (HCWs) Augusta, GA, USA, investigate any potential associations with ethno-demographic features. Specifically, aimed compare naturally infected individuals naïve understand dynamics after vaccination. A total of 290 HCWs were included assessed prospectively study. COVID status was determined using saliva-based assay. Neutralizing antibody (NAb) levels quantified chemiluminescent immunoassay system, IgG measured an enzyme-linked immunosorbent assay method. We examined among participants different statistical tests including logistic regression multiple correspondence analysis. Our findings revealed NAb at 8-12 months postvaccination. Furthermore, multivariable analysis indicated that more pronounced White (odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.07-4.08, p 0.02) (OR 2.07, CI 1.04-4.11, 0.03) whole cohort. Booster doses significantly increased levels, while observed without booster 12 results highlight importance understanding influence demographic factors waning immunity SARS-CoV-2. addition, our emphasize value ensure durable immunity.

Language: Английский

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Evidences support that dengue virus can impart broad‐spectrum immunity against betacoronaviruses in dengue endemic regions

Journal of Medical Virology, Journal Year: 2024, Volume and Issue: 96(6)

Published: June 1, 2024

Abstract COVID‐19 tended to be less aggressive in dengue endemic regions. Conversely, cases plummeted zones during the active years of pandemic (2020–2021). We and others have demonstrated serological cross‐reactivity between these two viruses different families. further that serum samples were cross‐reactive virus (DV) tests, “cross‐neutralized” all DV serotypes Huh7 cells. Here we showed by co‐immunoprecipitation (Co‐IP) atomic force microscopy (AFM) imaging severe acute respiratory syndrome (SARS)‐coronavirus (CoV)‐2 (SARS‐CoV‐2) spike (S) protein subunit S1 S2 monoclonal antibodies can indeed, bind particles. Likewise, envelope (DV E Abs) high docking frequency with other human pathogenic beta‐CoVs murine hepatitis virus‐1 (MHV‐1). SARS‐CoV‐2 Ab didn't show or Co‐IP MHV‐1 supporting poor cross‐protection among CoVs. Abs binding (AFM, Co‐IP, immunofluorescence) prepandemic patients' even plaques cell culture. Furthermore, marked inhibition potential a surrogate virus‐based competitive enzyme‐linked immunosorbent assay, used for determining neutralizing against S receptor‐binding domain samples. therefore, provide multiple evidence as why CoVs are epidemiologically prevalent highly regions globally.

Language: Английский

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Possible contribution of rare alleles of human ACE2 in the emergence of SARS-CoV-2 variants escaping the immune response

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 10, 2023

Since the start of SARS-CoV-2 pandemic, rapid replacement one lineage by another has been observed. Indeed, is evolving through a quasispecies mechanism leading to post-infection mutation selection under positive evolutionary pressure (host-driven viral evolution). These mutations may reduce effectiveness specific neutralizing immune response against virus. We provide here evidence that apart from variants system, cellular receptor can just as well select which escape neutralization.

Language: Английский

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Silent Symptoms, Active Immunity: Insights into Early-Stage Cytokine Expressions in Ugandan Mild and Asymptomatic COVID-19 subjects

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 9, 2023

Background This study examined the early response of individuals with mild and asymptomatic SARS-CoV-2 infection by analysing cytokine, chemokine, growth factor responses to CD4 CD8 cell stimulation, aiming understand immune expressions that might inform potential targets for immunotherapy interventions.Methods Between July November 2020, we assessed 15 individuals, predominantly males a median age 25. Of these, eight displayed symptoms, while seven were asymptomatic. We evaluated their T-cell stimulation measuring 48 unique cytokines, chemokines, factors. Random forest principal component analysis (PCA) methods utilized identify pivotal cytokines classify them according functional roles.Results Consistently low levels specific suggested minimal impact on activation processes, moderate concentrations others after or implied vital roles in modulation, recruitment activation, cytokine regulation, tissue healing. Optimal was achieved through balanced interplay between pro-inflammatory anti-inflammatory striking delicate equilibrium averted undue inflammation. A persistent marked consistent factors sustained over observation period. TGF-alpha, GRO-alpha, IL-6, IL-10 emerged as promising biomarkers symptom manifestation activation. Predictive analyses highlighted IL-8, G-CSF, MCP-1, EGF, MIP-1-alpha stimulating cells, MCP-1 IL-8 particularly displaying persistence.Conclusion research elucidates during initial phases COVID-19 infection. The outcomes enhance comprehension reactions offer valuable insights designing immunotherapies. Refining targeted can improve patient outcomes, manage viral infections, advance global health.

Language: Английский

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Clinical and laboratory considerations: determining an antibody-based composite correlate of risk for reinfection with SARS-CoV-2 or severe COVID-19

Frontiers in Public Health, Journal Year: 2023, Volume and Issue: 11

Published: Dec. 28, 2023

Much of the global population now has some level adaptive immunity to SARS-CoV-2 induced by exposure virus (natural infection), vaccination, or a combination both (hybrid immunity). Key questions that subsequently arise relate duration and protection an individual might expect based on their infection vaccination history. A multi-component composite correlate risk (CoR) could inform individuals stakeholders about aid decision making. This perspective evaluates various elements need be accommodated in development antibody-based CoR for reinfection with severe COVID-19, including variation dose, transmission route, viral genetic variation, patient factors, status. We provide overview antibody dynamics exploration specifics testing. further discuss anti-SARS-CoV-2 immunoassays, sample matrices, testing formats, frequency sampling optimal time point such sampling. While is challenging, we our recommendations each these key areas highlight require work undertaken.

Language: Английский

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