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

How unequal vaccine distribution promotes the evolution of vaccine escape DOI Creative Commons
Philip J. Gerrish, Fernando Saldaña, Benjamin Galeota-Sprung

et al.

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

Published: March 28, 2021

Abstract Health officials warn that SARS-CoV-2 vaccines must be uniformly distributed within and among countries if we are to quell the ongoing pandemic. Yet there has been little critical assessment of underlying reasons for this warning. Here, explicitly show why vaccine equity is necessary. Perhaps counter-intuitively, find escape mutants less likely come from highly vaccinated regions where strong selection pressure favoring more neighboring unvaccinated no escape. Unvaccinated geographic thus provide evolutionary reservoirs which new strains can arise cause epidemics beyond. Our findings have timely implications rollout strategies public health policy.

Language: Английский

Citations

10
Beyond the new normal: assessing the feasibility of vaccine-based elimination of SARS-CoV-2 DOI Creative Commons
Madison Stoddard, Sharanya Sarkar, Ryan P. Nolan

et al.

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

Published: Jan. 29, 2021

Abstract 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 elimination 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 do not prevent infection will allow extensive endemic spread upon social economic conditions. Vaccines only reduce symptomatic or mortality fail mitigate serious risks, particularly over-65 population, likely resulting hundreds thousands US deaths yearly basis. points possibility complete with high population-level compliance highly effective at reducing infection. Notably, vaccine-mediated reduction transmission critical elimination, order partially-effective play positive role other stackable (complementary) interventions must be deployed simultaneously.

Language: Английский

Citations

9
How unequal vaccine distribution promotes the evolution of vaccine escape DOI Creative Commons
Philip J. Gerrish, Fernando Saldaña, Benjamin Galeota-Sprung

et al.

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

Published: April 9, 2021

Abstract Health officials warn that SARS-CoV-2 vaccines must be uniformly distributed within and among countries if we are to quell the ongoing pandemic. Yet there has been little critical assessment of underlying reasons for this warning. Here, explicitly show why vaccine equity is necessary. Perhaps counter-intuitively, find escape mutants less likely come from highly vaccinated regions where strong selection pressure favoring more neighboring unvaccinated no escape. Unvaccinated geographic thus provide evolutionary reservoirs which new strains can arise cause epidemics beyond. Our findings have timely implications rollout strategies public health policy.

Language: Английский

Citations

8
From SARS-CoV-2 infection to COVID-19 morbidity: an in silico projection of virion flow rates to the lower airway via nasopharyngeal fluid boluses DOI Creative Commons
Saikat Basu,

Mohammad Mehedi Hasan Akash,

Natasha S. Hochberg

et al.

Rhinology online, Journal Year: 2022, Volume and Issue: 5(5), P. 10 - 18

Published: Jan. 27, 2022

Background: While the nasopharynx is initially dominant upper airway infection site for SARS-CoV-2, physiologic mechanism launching at lower still not well-understood. Based on rapidity of progression to lungs, it has been hypothesized that may be acting as primary seeding zone subsequent contamination via aspiration virus-laden boluses nasopharyngeal fluids. Methodology: To examine plausibility aspiration-driven mechanism, we have computationally tracked inhalation process in three anatomic reconstructions and quantified liquid volume transmitted airspace during each aspiration. Results: Extending numerical trends earlier records frequencies indicates a total aspirated 0.3 – 0.76 ml/day. Subsequently, mean sputum viral load, our modeling projects number virions reaching will range over 2.1×106 5.3×106 /day; peak corresponding hovers between 7.1×108 1.8×109. Conclusions: The virion transmission findings fill key piece mechanistic puzzle systemic subjectively point health conditions like dysphagia, with proclivity increased aspiration, some potential underlying risk factors aggressive lung infections.

Language: Английский

Citations

5
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.

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

Published: Feb. 12, 2021

Coronaviruses have caused several epidemics and pandemics including the ongoing coronavirus disease 2019 (COVID-19). Some prophylactic vaccines therapeutic antibodies already showed striking effectiveness against COVID-19. Nevertheless, concerns remain about antigenic drift in SARS-CoV-2 as well threats from other sarbecoviruses. Cross-neutralizing to SARS-related viruses provide opportunities address such concerns. Here, we report on crystal structures of a cross-neutralizing antibody CV38-142 complex with receptor binding domains SARS-CoV. Our structural findings mechanistic insights into how this can accommodate variation these viruses. synergizes antibodies, particular COVA1-16, enhance neutralization Overall, study provides valuable information for vaccine design current future protect zoonotic coronaviruses.

Language: Английский

Citations

6
Pandemic response: Isolationism or solidarity? DOI
Philip J. Gerrish, Fernando Saldaña, Alexandre Colato

et al.

Elsevier eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 93 - 108

Published: Jan. 1, 2023

Language: Английский

Citations

2
From SARS-CoV-2 infection to COVID-19 disease: a proposed mechanism for viral spread to the lower airway based on in silico estimation of virion flow rates DOI Open Access
Saikat Basu, Arijit Chakravarty

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2020, Volume and Issue: unknown

Published: Dec. 22, 2020

ABSTRACT While the nasopharynx in upper respiratory airway is dominant initial infection site for SARS-CoV-2, physiologic mechanism that launches lower still not well-understood. Based on rapidity with which SARS-CoV-2 progresses to lungs, it has been conjectured acts as seeding zone subsequent contamination of via aspiration virus-laden boluses nasopharyngeal fluids. In this study, we examine plausibility proposed mechanism. To end, have developed computational fluid mechanics models inhalation process two medical imaging based reconstructions and quantified liquid volume ingested into airspace during each aspiration. The numerical predictions are validated by comparing number projected aspirations (approximately 2 – 4) an eight-hour sleep cycle prior observational findings 3 human subjects. Extending trends earlier records frequency entire day indicates a total aspirated 0.3 0.76 ml per day. We then used sputum assessment data from hospitalized COVID-19 patients estimate virions transmitted daily lungs boluses. For mean viral load, our modeling projects penetrating will range over 2.1 × 10 6 5.3 ; peak corresponding hovers between 7.1 8 17.9 . These fill key piece mechanistic puzzle progression development disease within patient, point dysphagia potential underlying risk factor COVID-19. also significant practical implications design prophylactics therapeutics aim constrain pathogenic progress limits airway.

Language: Английский

Citations

5
Immunogenic Amino Acid Motifs and Linear Epitopes of COVID-19 mRNA Vaccines DOI Open Access
Adam V. Wisnewski, Carrie A. Redlich, Kathy Kamath

et al.

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

Published: May 25, 2021

ABSTRACT 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 N=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

4
The gray swan: model-based assessment of the risk of sudden failure of hybrid immunity to SARS-CoV-2 DOI Creative Commons
Madison Stoddard, Yuan Lin, Sharanya Sarkar

et al.

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

Published: March 1, 2023

Abstract In the fourth year of COVID-19 pandemic, public health authorities worldwide have adopted a strategy learning to live with SARS-CoV-2. This has involved removal measures for limiting viral spread, resulting in large burden recurrent SARS-CoV-2 infections. Crucial managing this is concept so-called wall hybrid immunity, through repeated reinfections and vaccine boosters, reduce risk severe disease death. Protection against both infection provided by induction neutralizing antibodies (nAbs) However, pharmacokinetic (PK) waning rapid evolution degrade nAb binding titers. The recent emergence variants strongly immune evasive potential vaccinal natural responses raises question whether population-level immunity can be maintained face jumps potency. Here we use an agent-based simulation address question. Our findings suggest may cause failure population sudden increases mortality. As rise mortality will only become apparent weeks following wave disease, reactive strategies not able provide meaningful mitigation. Learning virus could thus lead death tolls very little warning. work points importance proactive management ongoing need multifactorial approaches control.

Language: Английский

Citations

1
Development and pre-clinical evaluation of Newcastle disease virus-vectored SARS-CoV-2 intranasal vaccine candidate DOI Creative Commons
Manolo Fernández‐Díaz, Katherine Calderón, Aldo Rojas-Neyra

et al.

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

Published: March 8, 2021

ABSTRACT The COVID-19 pandemic has claimed the lives of millions people worldwide and threatens to become an endemic problem, therefore need for as many types vaccines possible is high importance. Because doses required, it desirable that are not only safe effective, but also easy administer, store, inexpensive produce. Newcastle Disease Virus (NDV) responsible a respiratory disease in chickens. It no pathogenic homologue humans. NDV recognized oncolytic virus, its use humans oncological treatment being evaluated. In present work, we have developed two NDV-vectored candidate vaccines, which carry surface-exposed RBD S1 antigens SARS-CoV-2, respectively. These vaccine candidates were produced specific-pathogen-free embryonating chicken eggs, purified from allantoic fluid before lyophilization. administered intranasally three different animal models: mice, rats hamsters, evaluated safety, toxicity, immunogenicity, stability efficacy. Efficacy was challenge assay against active SARS-CoV-2 virus Golden Syrian hamster model. based on antigen shown be highly immunogenic, with ability neutralize in-vitro , even extreme dilution 1/640. Our results reveal this protects lungs animals, preventing cellular damage tissue. addition, reduces viral load lungs, suggesting may significantly reduce likelihood transmission. Being lyophilized, very stable can stored several months at 4-8⁰C. conclusion, our NDV-based favorable performance pre-clinical study, serving evidence future evaluation Phase-I human clinical trial. This represents promising tool fight COVID-19.

Language: Английский

Citations

3