scholarly journals Newcastle Disease Virus-Like Particles Displaying Prefusion-Stabilized SARS-CoV-2 Spikes Elicit Potent Neutralizing Responses

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 73 ◽  
Author(s):  
Yongping Yang ◽  
Wei Shi ◽  
Olubukola M. Abiona ◽  
Alexandra Nazzari ◽  
Adam S. Olia ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
Geometric Mean ◽  
Virus Like Particles ◽  
Negative Stain ◽  
Molar Equivalent ◽  
Boost Immunization ◽  
Negative Stain Electron Microscopy

The COVID-19 pandemic highlights an urgent need for vaccines that confer protection from SARS-CoV-2 infection. One approach to an effective COVID-19 vaccine may be through the display of SARS-CoV-2 spikes on the surface of virus-like particles, in a manner structurally mimicking spikes on a native virus. Here we report the development of Newcastle disease virus-like particles (NDVLPs) displaying the prefusion-stabilized SARS-CoV-2 spike ectodomain (S2P). Immunoassays with SARS-CoV-2-neutralizing antibodies revealed the antigenicity of S2P-NDVLP to be generally similar to that of soluble S2P, and negative-stain electron microscopy showed S2P on the NDVLP surface to be displayed with a morphology corresponding to its prefusion conformation. Mice immunized with S2P-NDVLP showed substantial neutralization titers (geometric mean ID50 = 386) two weeks after prime immunization, significantly higher than those elicited by a molar equivalent amount of soluble S2P (geometric mean ID50 = 17). Neutralizing titers at Week 5, two weeks after a boost immunization with S2P-NDVLP doses ranging from 2.0 to 250 μg, extended from 2125 to 4552, and these generally showed a higher ratio of neutralization versus ELISA than observed with soluble S2P. Overall, S2P-NDVLP appears to be a promising COVID-19 vaccine candidate capable of eliciting substantial neutralizing activity.

scholarly journals Requirements for the Assembly and Release of Newcastle Disease Virus-Like Particles

2006 ◽  
Vol 80 (22) ◽  
pp. 11062-11073 ◽  
Author(s):  
Homer D. Pantua ◽  
Lori W. McGinnes ◽  
Mark E. Peeples ◽  
Trudy G. Morrison
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Plasma Membranes ◽  
Matrix Protein ◽  
Viral Proteins ◽  
M Protein ◽  
Virion Assembly ◽  
Virus Like Particles ◽  
Necessary And Sufficient

ABSTRACT Paramyxoviruses, such as Newcastle disease virus (NDV), assemble in and bud from plasma membranes of infected cells. To explore the role of each of the NDV structural proteins in virion assembly and release, virus-like particles (VLPs) released from avian cells expressing all possible combinations of the nucleoprotein (NP), membrane or matrix protein (M), an uncleaved fusion protein (F-K115Q), and hemagglutinin-neuraminidase (HN) protein were characterized for densities, protein content, and efficiencies of release. Coexpression of all four proteins resulted in the release of VLPs with densities and efficiencies of release (1.18 to 1.16 g/cm3 and 83.8% ± 1.1%, respectively) similar to those of authentic virions. Expression of M protein alone, but not NP, F-K115Q, or HN protein individually, resulted in efficient VLP release, and expression of all different combinations of proteins in the absence of M protein did not result in particle release. Expression of any combination of proteins that included M protein yielded VLPs, although with different densities and efficiencies of release. To address the roles of NP, F, and HN proteins in VLP assembly, the interactions of proteins in VLPs formed with different combinations of viral proteins were characterized by coimmunoprecipitation. The colocalization of M protein with cell surface F and HN proteins in cells expressing all combinations of viral proteins was characterized. Taken together, the results show that M protein is necessary and sufficient for NDV budding. Furthermore, they suggest that M-HN and M-NP interactions are responsible for incorporation of HN and NP proteins into VLPs and that F protein is incorporated indirectly due to interactions with NP and HN protein.

Titration of Newcastle disease virus and its neutralizing antibodies in microplates by a modified hemadsorption and hemadsorption inhibition method

1976 ◽  
Vol 3 (3) ◽  
pp. 227-232
Author(s):  
Israel Institute for Biological Research, Ness-Ziona, Israel
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Chicken Embryo ◽  
Neutralizing Antibodies ◽  
Inhibition Test ◽  
Virus Infectivity ◽  
Embryo Fibroblasts ◽  
Microneutralization Test ◽  
Chicken Embryo Fibroblasts

Using the microtiter system, titration of Newcastle disease virus infectivity and neutralizing antibodies was carried out in chicken embryo fibroblasts grown in "U" or flat-bottomed plates. Infectivity was detected by a combined hemadsorption-hemagglutination method. Inhibition of that reaction indicated the presence of neutralizing antibodies. A 24-h microneutralization test was developed and compared to the plaque neutralization and microhemagglutination inhibition test. Reproducibility of the microneutralization test was statistically analyzed.

scholarly journals A Newcastle disease virus (NDV) expressing membrane-anchored spike as a cost-effective inactivated SARS-CoV-2 vaccine

2020 ◽  
Author(s):  
Weina Sun ◽  
Stephen McCroskery ◽  
Wen-Chun Liu ◽  
Sarah R. Leist ◽  
Yonghong Liu ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Low Cost ◽  
Production Capacity ◽  
Cost Effective ◽  
Influenza Virus Vaccine ◽  
Global Scale

A successful SARS-CoV-2 vaccine must be not only safe and protective but must also meet the demand on a global scale at low cost. Using the current influenza virus vaccine production capacity to manufacture an egg-based inactivated Newcastle disease virus (NDV)/SARS-CoV-2 vaccine would meet that challenge. Here, we report pre-clinical evaluations of an inactivated NDV chimera stably expressing the membrane-anchored form of the spike (NDV-S) as a potent COVID-19 vaccine in mice and hamsters. The inactivated NDV-S vaccine was immunogenic, inducing strong binding and/or neutralizing antibodies in both animal models. More importantly, the inactivated NDV-S vaccine protected animals from SARS-CoV-2 infections or significantly attenuated SARS-CoV-2 induced disease. In the presence of an adjuvant, antigen-sparing could be achieved, which would further reduce the cost while maintaining the protective efficacy of the vaccine.

scholarly journals Safety and Immunogenicity of an Inactivated Recombinant Newcastle Disease Virus Vaccine Expressing SARS-CoV-2 Spike: Interim Results of a Randomised, Placebo-Controlled, Phase 1/2 Trial

2021 ◽  
Author(s):  
Punnee Pitisuttithum ◽  
Viravarn Luvira ◽  
Saranath Lawpoolsri ◽  
Sant Muangnoicharoen ◽  
Supitcha Kamolratanakul ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Virus Vaccine ◽  
Newcastle Disease ◽  
Phase 1 ◽  
Geometric Mean ◽  
Vaccine Trial ◽  
Pseudotyped Virus ◽  
Link Type ◽  
Newcastle Disease Virus Vaccine

SummaryBackgroundProduction of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It’s being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.MethodsThis phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov (NCT04764422).FindingsBetween March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation’s immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 IU/mL (1 µg, 95% CI 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥4-fold increase over baseline.InterpretationNDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.FundingNational Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA)

scholarly journals Immunoinformatics analysis and antibody epitope comparison of Newcastle disease virus classical vaccines with a virus involved in the fifth NDV panzootic

2021 ◽  
Author(s):  
Seyed-Elias Tabatabaeizadeh
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Vaccine Strain ◽  
Newcastle Disease ◽  
Neutralizing Antibodies ◽  
3D Structure ◽  
Live Vaccines ◽  
Field Virus ◽  
Inactivated Vaccines ◽  
Antibody Epitopes

Abstract Newcastle disease virus (NDV) has negatively affected the poultry industry worldwide. Given that the antigenic similarity of a vaccine strain to a field virus is effective in protection, an immunoinformatics study was performed to examine the similarity between antibody epitopes of classical vaccines and a sub-genotype VII.2 NDV (VII.2 NDV). Considering the role of fusion (F) and hemagglutinin-neuraminidase (HN) proteins in the induction of neutralizing antibodies, the 3D structure of HN and F proteins of the VII.2 NDV and nine vaccine strains were predicted, refined, and validated. Using these structures, linear and conformational antibody epitopes were mapped. Epitope analysis showed distinct results from the evolutionary distance and protein identity analysis and it was found that the range of difference in the number of identical epitopes in relation to F is wider than HN protein. LaSota and B1 vaccine strains showed the least epitope identity to the VII.2 NDV. The V4 and I-2 vaccine strains showed the highest epitope identity with the VII.2 NDV especially in F protein which is important in virus cell-to-cell transmission. In conclusion, excellence of the LaSota vaccine under field condition shows that protection is not just about epitope similarities and especially in the case of live vaccines, the vaccine-induced damage, replicative capacity and tropism of the vaccine strain are important. The prediction of this study may be useful for inactivated vaccines in which the amount of antigen is all that matters.

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