A single dose of recombinant VSV-∆G-spike vaccine provides protection against SARS-CoV-2 challenge

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Dec. 16, 2020

Abstract The COVID-19 pandemic caused by SARS-CoV-2 imposes an urgent need for rapid development of efficient and cost-effective vaccine, suitable mass immunization. Here, we show the a replication competent recombinant VSV-∆G-spike in which glycoprotein VSV is replaced spike protein SARS-CoV-2. In-vitro characterization this vaccine indicates expression presentation on viral membrane with antigenic similarity to A golden Syrian hamster in-vivo model implemented. We that single-dose vaccination results potent induction neutralizing antibodies. Importantly, protects hamsters against challenge, as demonstrated abrogation body weight loss, alleviation extensive tissue damage loads lungs nasal turbinates. Taken together, suggest safe, efficacious protective

Language: Английский

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Smallpox and Vaccinia

Elsevier eBooks, Journal Year: 2017, Volume and Issue: unknown, P. 1001 - 1030.e12

Published: July 21, 2017

Language: Английский

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Battle Royale: Innate Recognition of Poxviruses and Viral Immune Evasion

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 765 - 765

Published: July 1, 2021

Host pattern recognition receptors (PRRs) sense pathogen-associated molecular patterns (PAMPs), which are signatures shared by different pathogens. Recognition of PAMPs PRRs initiate innate immune responses via diverse signaling pathways. Over recent decades, advances in our knowledge sensing have enhanced understanding the host response to poxviruses. Multiple PRR families been implicated poxvirus detection, mediating initiation cascades, activation transcription factors, and, ultimately, expression antiviral effectors. To counteract defense, poxviruses evolved a variety immunomodulators that strategies disrupt or circumvent triggered PRRs. These interactions influence outcomes infections. This review focuses on current roles poxviruses, their elicited effector functions, and how poxviral antagonize PRR-mediated responses.

Language: Английский

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Monkeypox: Immune response, vaccination and preventive efforts

Narra J, Journal Year: 2022, Volume and Issue: 2(3)

Published: Oct. 21, 2022

Infectious threats to humans are continuously emerging. The 2022 worldwide monkeypox outbreak is the latest of these with virus rapidly spreading 106 countries by end September 2022. burden ongoing manifested 68,000 cumulative confirmed cases and 26 deaths. Although usually a self-limited disease, patients can suffer from extremely painful skin lesions complications occur reported mortalities. antigenic similarity between smallpox (variola virus) be utilized prevent using vaccines; treatment also based on antivirals initially designed treat smallpox. However, further studies needed fully decipher immune response evasion mechanisms. In this review we provide an up-to-date discussion current state knowledge regarding special focus innate response, mechanisms vaccination against virus.

Language: Английский

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In-silico formulation of a next-generation polyvalent vaccine against multiple strains of monkeypox virus and other related poxviruses

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0300778 - e0300778

Published: May 17, 2024

Mpox (formerly known as monkeypox) virus and some related poxviruses including smallpox pose a significant threat to public health, effective prevention treatment strategies are needed. This study utilized reverse vaccinology approach retrieve conserved epitopes for monkeypox construct vaccine that could provide cross-protection against viruses with similar antigenic properties. The selected virulent proteins of virus, MPXVgp165, Virion core protein P4a, were subjected epitope mapping construction. Two vaccines constructed using T cell B PADRE human beta-defensins adjuvants conjugated in the sequence. Both constructs found be highly antigenic, non-allergenic, nontoxic, soluble, suggesting their potential generate an adequate immune response safe humans. Vaccine 1 was molecular dynamic simulation studies. studies revealed TLR8-vaccine complex more stable than TLR3-vaccine complex. lower RMSD RMSF values TLR8 bound compared TLR3 suggested better stability consistency hydrogen bonds. Rg chain indicated overall stability, whereas showed deviations throughout simulation. These results suggest preventive measure however, further experimental validation is required confirm these findings.

Language: Английский

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Confronting the threat of bioterrorism: realities, challenges, and defensive strategies

The Lancet Infectious Diseases, Journal Year: 2018, Volume and Issue: 19(1), P. e2 - e13

Published: Oct. 16, 2018

Language: Английский

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Induction of Innate Immune Response by TLR3 Agonist Protects Mice against SARS-CoV-2 Infection

Viruses, Journal Year: 2022, Volume and Issue: 14(2), P. 189 - 189

Published: Jan. 19, 2022

SARS-CoV-2, a member of the coronavirus family, is causative agent COVID-19 pandemic. Currently, there still an urgent need in developing efficient therapeutic intervention. In this study, we aimed at evaluating effect single intranasal treatment TLR3/MDA5 synthetic agonist Poly(I:C) against lethal dose SARS-CoV-2 K18-hACE2 transgenic mice. We demonstrate here that early acts synergistically with to induce intense, immediate and transient upregulation innate immunity-related genes lungs. This accompanied by viral load reduction, lung brain cytokine storms prevention increased levels macrophages NK cells, resulting 83% mice survival, concomitantly long-term immunization. Thus, priming immunity or alike may provide immediate, safe protective measure infection.

Language: Английский

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Challenges and Achievements in Prevention and Treatment of Smallpox

Vaccines, Journal Year: 2018, Volume and Issue: 6(1), P. 8 - 8

Published: Jan. 29, 2018

Declaration of smallpox eradication by the WHO in 1980 led to discontinuation worldwide vaccination campaign. The increasing percentage unvaccinated individuals, existence its causative infectious agent variola virus (VARV), and recent synthetic achievements increase threat intentional or accidental release reemergence smallpox. Control would require an emergency campaign, as no other protective measure has been approved achieve ensure protection. Experimental data surrogate animal models support assumption, based on anecdotal, uncontrolled historical data, that up 4 days postexposure confers effective long incubation period, uncertainty exposure status surrounding population, call for development evaluation safe methods enabling extension therapeutic window, reduce disease manifestations vaccine adverse reactions. To these goals, we need evaluate efficacy novel already licensed vaccines a sole treatment, conjunction with immune modulators antiviral drugs. In this review, address available achievements, open questions.

Language: Английский

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Synergistic effect of two human-like monoclonal antibodies confers protection against orthopoxvirus infection

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 16, 2024

Abstract The eradication of smallpox was officially declared by the WHO in 1980, leading to discontinuation vaccination campaign against virus. Consequently, immunity and related orthopoxviruses like Monkeypox virus gradually declines, highlighting need for efficient countermeasures not only prevention, but also treatment already exposed individuals. We have recently developed human-like monoclonal antibodies (mAbs) from vaccinia virus-immunized non-human primates. Two mAbs, MV33 EV42, targeting two infectious forms virus, were selected vivo evaluation, based on their vitro neutralization potency. A single dose either or EV42 administered three days post-infection (dpi) BALB/c female mice provides full protection lethal ectromelia challenge. Importantly, a combination both mAbs confers even when provided five dpi. Whole-body bioimaging viral load analysis reveal that allows faster more clearance target organs compared separately. combined further post-exposure currently circulating Cast/EiJ mice, therapeutic potential other orthopoxviruses.

Language: Английский

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Induction of Superior Systemic and Mucosal Protective Immunity to SARS-CoV-2 by Nasal Administration of a VSV–ΔG–Spike Vaccine

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 491 - 491

Published: May 1, 2024

The emergence of rapidly spreading variants Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) poses a major challenge to vaccines’ protective efficacy. Intramuscular (IM) vaccine administration induces short-lived immunity but does not prevent infection and transmission. New vaccination strategies are needed extend the longevity protection, induce mucosal systemic viral intranasal (IN) VSV–ΔG–spike candidate directly surfaces yielded superior at lower doses. Compared IM in K18–hACE2 model, IN preferentially induced IgA T-cells, reduced load site infection, ameliorated disease-associated brain gene expression. was even one year after administration. As most world population has been vaccinated by injection, we demonstrate potential heterologous + regimen while maintaining immunity. Furthermore, prevented virus transmission golden Syrian hamster co-caging model. Taken together, show that with VSV–ΔG–spike, either as homologous or boost following vaccination, favorable over inducing efficient immunity, long-term protection preventing

Language: Английский

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