Preclinical Evaluation of a Newcastle Disease Virus-Vectored Intranasal SARS-CoV-2 Vaccine DOI Creative Commons
Manolo Fernández‐Díaz, Katherine Calderón, Aldo Rojas-Neyra

et al.

Research Square (Research Square), Journal Year: 2021, Volume and Issue: unknown

Published: April 27, 2021

Abstract The COVID-19 pandemic has claimed the lives of millions people. Vaccination is a critical tool for control transmission; however, recent emergence potentially vaccine-resistant variants renders it important to have range vaccines types. It desirable that are safe, effective, easy administer and store, inexpensive produce. Newcastle disease virus (NDV), responsible respiratory in chickens, no pathogenic homologue humans. We developed two types NDV-vectored candidate vaccines, evaluated them SARS-CoV-2 challenge hamsters. Vaccinations resulted generation neutralizing antibodies, prevented lung damage, reduced viral load viability. In conclusion, our NDV-based vaccine performed well warrants evaluation Phase I human clinical trial. This represents promising fight against COVID-19.

Language: Английский

Neutralising antibody escape of SARS‐CoV‐2 spike protein: Risk assessment for antibody‐based Covid‐19 therapeutics and vaccines DOI Open Access
Daniele Focosi, Fabrizio Maggi

Reviews in Medical Virology, Journal Year: 2021, Volume and Issue: 31(6)

Published: March 16, 2021

The Spike protein is the target of both antibody-based therapeutics (convalescent plasma, polyclonal serum, monoclonal antibodies) and vaccines. Mutations in could affect efficacy those treatments. Hence, monitoring mutations necessary to forecast readapt inventory therapeutics. Different phylogenetic nomenclatures have been used for currently circulating SARS-CoV-2 clades. has different hotspots mutation deletion, most dangerous immune escape being ones within receptor binding domain (RBD), such as K417N/T, N439K, L452R, Y453F, S477N, E484K, N501Y. Convergent evolution led combinations among In this review we focus on main variants concern, that is, so-called UK (B.1.1.7), South African (B.1.351) Brazilian (P.1) strains.

Language: Английский

Citations

162
A combination of cross-neutralizing antibodies synergizes to prevent SARS-CoV-2 and SARS-CoV pseudovirus infection DOI Creative Commons

Hejun Liu,

Meng Yuan, Deli Huang

et al.

Cell Host & Microbe, Journal Year: 2021, Volume and Issue: 29(5), P. 806 - 818.e6

Published: April 16, 2021

Language: Английский

Citations

65
Analysis of Immune Escape Variants from Antibody-Based Therapeutics against COVID-19: A Systematic Review DOI Open Access
Daniele Focosi, Fabrizio Maggi, Massimo Franchini

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 23(1), P. 29 - 29

Published: Dec. 21, 2021

The accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports documented immune escape after treatment monoclonal antibodies and COVID-19-convalescent plasma (CCP). While the former mainly associated specific single amino acid mutations at residues within receptor-binding domain (e.g., E484K/Q, Q493R, S494P), few cases evasion CCP were recurrent deletions N-terminal spike protein ΔHV69-70, ΔLGVY141-144 ΔAL243-244). continuous genomic monitoring non-responders needed to better understand frequencies fitness emerging variants.

Language: Английский

Citations

56
Predicting the zoonotic capacity of mammals to transmit SARS-CoV-2 DOI Creative Commons
Ilya R. Fischhoff, Adrian A. Castellanos, João Rodrigues

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Feb. 19, 2021

Abstract Back and forth transmission of SARS-CoV-2 between humans animals may lead to wild reservoirs virus that can endanger efforts toward long-term control COVID-19 in people, protecting vulnerable animal populations are particularly susceptible lethal disease. Predicting high risk host species is key targeting field surveillance lab experiments validate zoonotic potential. A major bottleneck predicting hosts the small number with available molecular information about structure ACE2, a cellular receptor required for viral cell entry. We overcome this by combining species’ ecological biological traits 3D modeling protein interactions using machine learning methods. This approach enables predictions capacity over 5,000 mammals — an order magnitude more than previously possible. The accuracy achieved strongly corroborated vivo empirical studies. identify numerous common mammal whose predicted close proximity further enhance spillover spillback SARS-CoV-2. Our results reveal priority areas geographic overlap global hotspots potential new With sequence data only fraction species, predictive integrating across multiple scales offers conceptual advance expand our viruses similarly unknown potentially broad ranges.

Language: Английский

Citations

29
Polyclonal hyper immunoglobulin: A proven treatment and prophylaxis platform for passive immunization to address existing and emerging diseases DOI Creative Commons

Tharmala Tharmalingam,

Xiaobing Han,

Ashley Wozniak

et al.

Human Vaccines & Immunotherapeutics, Journal Year: 2021, Volume and Issue: 18(2)

Published: May 19, 2021

Passive immunization with polyclonal hyper immunoglobulin (HIG) therapy represents a proven strategy by transferring immunoglobulins to patients confer immediate protection against range of pathogens including infectious agents and toxins. Distinct from active immunization, the is passive will clear system; therefore, administration an effective dose must be maintained for prophylaxis or treatment until natural adaptive immune response mounted pathogen/agent cleared. The current review provides overview this technology, key considerations address different pathogens, suggested improvements. reflect on learnings development HIGs in public health threats due Zika, influenza, severe acute respiratory syndrome coronavirus 2.

Language: Английский

Citations

24
The Impact of Vaccination Frequency on COVID-19 Public Health Outcomes: A Model-Based Analysis DOI Creative Commons
Lin Yuan, Madison Stoddard, Sharanya Sarkar

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(4), P. 368 - 368

Published: March 30, 2025

Background: While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on ongoing COVID-19 pandemic, viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, manufacturers public health authorities number options at their disposal to maximize benefits vaccination. In particular, effect booster schedules performance bears further study. Methods: To better understand performance, we used an agent-based modeling framework population pharmacokinetic model simulate boosting frequency durability protection against infection severe acute disease. Results: Our work suggests that repeated dosing frequent intervals (three or more times year) may offset degradation efficacy, preserving utility in managing pandemic. Conclusions: Given practical significance potential improvements utility, clinical research effects vaccination would be highly impactful. These findings are particularly relevant as worldwide reduced boosters once year less.

Language: Английский

Citations

0
Beyond the new normal: Assessing the feasibility of vaccine-based suppression of SARS-CoV-2 DOI Creative Commons
Madison Stoddard, Sharanya Sarkar, Yuan Lin

et al.

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(7), P. e0254734 - e0254734

Published: July 16, 2021

As the COVID-19 pandemic drags into its second year, there is hope on horizon, in form of SARS-CoV-2 vaccines which promise disease suppression and a return to pre-pandemic normalcy. In this study we critically examine basis for that hope, using an epidemiological modeling framework establish link between vaccine characteristics effectiveness bringing end unprecedented public health crisis. Our findings suggest social economic conditions without fully suppressing will lead extensive viral spread, resulting high burden even presence reduce risk infection mortality. points feasibility complete with population-level compliance are highly effective at reducing infection. Notably, vaccine-mediated reduction transmission critical suppression, order partially-effective play positive role complementary biomedical interventions measures must be deployed simultaneously.

Language: Английский

Citations

15
Immunogenic amino acid motifs and linear epitopes of COVID-19 mRNA vaccines DOI Creative Commons
Adam V. Wisnewski, Carrie A. Redlich,

Jian Liu

et al.

PLoS ONE, Journal Year: 2021, Volume and Issue: 16(9), P. e0252849 - e0252849

Published: Sept. 9, 2021

Reverse vaccinology is an evolving approach for improving vaccine effectiveness and minimizing adverse responses by limiting immunizations to critical epitopes. Towards this goal, we sought identify immunogenic amino acid motifs linear epitopes of the SARS-CoV-2 spike protein that elicit IgG in COVID-19 mRNA recipients. Paired pre/post vaccination samples from N = 20 healthy adults, post-vaccine additional 13 individuals were used immunoprecipitate targets expressed a bacterial display random peptide library, preferentially recognized peptides mapped primary sequence. The data several distinct vaccine-induced IgG, subset those targeted natural infection, which may mimic 3-dimensional conformation (mimotopes). Dominant identified C-terminal domains S1 S2 subunits (aa 558-569, 627-638, 1148-1159) have been previously associated with neutralization vitro demonstrate identity bat coronavirus SARS-CoV, but limited homology non-pathogenic human coronavirus. should be considered context variants, immune escape therapy design moving forward.

Language: Английский

Citations

12
ANALYSIS OF IMMUNE ESCAPE VARIANTS FROM ANTIBODY-BASED THERAPEUTICS AGAINST COVID-19 DOI Open Access
Daniele Focosi, Fabrizio Maggi, Massimo Franchini

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2021, Volume and Issue: unknown

Published: Nov. 11, 2021

Abstract Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports documented immune escape after treatment monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former mainly associated specific single amino acid mutations at residues within receptor-binding domain (e.g., E484K/Q, Q493R, S494P), few cases evasion CCP were recurrent deletions N-terminal Spike protein (e.g, ΔHV69-70, ΔLGVY141-144 ΔAL243-244). Continuous genomic monitoring non-responders needed to better understand frequencies fitness emerging variants.

Language: Английский

Citations

12
The impact of vaccination frequency on COVID-19 public health outcomes: A model-based analysis DOI Creative Commons
Madison Stoddard, Yuan Lin, Sharanya Sarkar

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 29, 2023

Abstract While the rapid deployment of SARS-CoV-2 vaccines had a significant impact on ongoing COVID-19 pandemic, viral immune evasion and waning neutralizing antibody titers have degraded vaccine efficacy. Nevertheless, manufacturers public health authorities number levers at their disposal to maximize benefits vaccination. Here, we use an agent-based modeling framework coupled with outputs population pharmacokinetic model examine boosting frequency durability vaccinal response Our work suggests that repeated dosing frequent intervals (multiple times year) may offset degradation efficacy, preserving utility in managing pandemic. relies assumptions about accumulation tolerability doses. Given practical significance potential improvements utility, clinical research better understand effects vaccination would be highly impactful. These findings are particularly relevant as worldwide seek reduce boosters once year or less. recommendations for draws attention possibility outcomes remain within reach.

Language: Английский

Citations

4