scholarly journals Newcastle Disease Virus as a Vaccine Vector for SARS-CoV-2

Pathogens ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 619
Author(s):  
Edris Shirvani ◽  
Siba K. Samal
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Vaccine Vector ◽  
Effective Vaccine ◽  
Vaccine Strategy ◽  
Vaccine Platform ◽  
Vector Vaccine ◽  
Advantages And Disadvantages ◽  
Avian Virus

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in more than 16 million infections and more than 600,000 deaths worldwide. There is an urgent need to develop a safe and effective vaccine against SARS-CoV-2. Currently, several strategies are being pursued to develop a safe and effective SARS-CoV-2 vaccine. However, each vaccine strategy has distinct advantages and disadvantages. Therefore, it is important to evaluate multiple vaccine platforms to select the most efficient vaccine platform for SARS-CoV-2. In this regard, Newcastle disease virus (NDV), an avian virus, has several well-suited properties for development of a vector vaccine against SARS-CoV-2. Here, we elaborate on the idea of considering NDV as a vaccine vector for SARS-CoV-2.

scholarly journals Mucosal Immunization with Newcastle Disease Virus Vector Coexpressing HIV-1 Env and Gag Proteins Elicits Potent Serum, Mucosal, and Cellular Immune Responses That Protect against Vaccinia Virus Env and Gag Challenges

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Sunil K. Khattar ◽  
Vinoth Manoharan ◽  
Bikash Bhattarai ◽  
Celia C. LaBranche ◽  
David C. Montefiori ◽  
...  
Keyword(s):  
Immune Responses ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Effective Vaccine ◽  
Gag Proteins ◽  
Humoral Immune ◽  
Vaccinia Viruses ◽  
Mucosal Immune Responses ◽  
Hiv 1

ABSTRACT Newcastle disease virus (NDV) avirulent strain LaSota was used to coexpress gp160 Env and p55 Gag from a single vector to enhance both Env-specific and Gag-specific immune responses. The optimal transcription position for both Env and Gag genes in the NDV genome was determined by generating recombinant NDV (rNDV)-Env-Gag (gp160 located between the P and M genes and Gag between the HN and L genes), rNDV-Gag-Env (Gag located between the P and M genes and gp160 between the HN and L genes), rNDV-Env/Gag (gp160 followed by Gag located between the P and M genes), and rNDV-Gag/Env (Gag followed by gp160 located between the P and M genes). All the recombinant viruses replicated at levels similar to those seen with parental NDV in embryonated chicken eggs and in chicken fibroblast cells. Both gp160 and Gag proteins were expressed at high levels in cell culture, with gp160 found to be incorporated into the envelope of NDV. The Gag and Env proteins expressed by all the recombinants except rNDV-Env-Gag self-assembled into human immunodeficiency virus type 1 (HIV-1) virus-like particles (VLPs). Immunization of guinea pigs by the intranasal route with these rNDVs produced long-lasting Env- and Gag-specific humoral immune responses. The Env-specific humoral and mucosal immune responses and Gag-specific humoral immune responses were higher in rNDV-Gag/Env and rNDV-Env/Gag than in the other recombinants. rNDV-Gag/Env and rNDV-Env/Gag were also more efficient in inducing cellular as well as protective immune responses to challenge with vaccinia viruses expressing HIV-1 Env and Gag in mice. These results suggest that vaccination with a single rNDV coexpressing Env and Gag represents a promising strategy to enhance immunogenicity and protective efficacy against HIV. IMPORTANCE A safe and effective vaccine that can induce both systemic and mucosal immune responses is needed to control HIV-1. In this study, we showed that coexpression of Env and Gag proteins of HIV-1 performed using a single Newcastle disease virus (NDV) vector led to the formation of HIV-1 virus-like particles (VLPs). Immunization of guinea pigs with recombinant NDVs (rNDVs) elicited potent long-lasting systemic and mucosal immune responses to HIV. Additionally, the rNDVs were efficient in inducing cellular immune responses to HIV and protective immunity to challenge with vaccinia viruses expressing HIV Env and Gag in mice. These results suggest that the use of a single NDV expressing Env and Gag proteins simultaneously is a novel strategy to develop a safe and effective vaccine against HIV.

scholarly journals High-level expression of a foreign gene from the most 3′-proximal locus of a recombinant Newcastle disease virus

2001 ◽  
Vol 82 (7) ◽  
pp. 1729-1736 ◽  
Author(s):  
Zhuhui Huang ◽  
Sateesh Krishnamurthy ◽  
Aruna Panda ◽  
Siba K. Samal
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Vaccine Vector ◽  
Foreign Gene ◽  
Gene Encoding ◽  
Reading Frame ◽  
Virulent Newcastle Disease Virus ◽  
Nucleocapsid Protein Gene ◽  
High Level

A previous report showed that insertion of a foreign gene encoding chloramphenicol acetyltransferase (CAT) between the HN and L genes of the full-length cDNA of a virulent Newcastle disease virus (NDV) yielded virus with growth retardation and attenuation. The NDV vector used in that study was pathogenic to chickens; it is therefore not suitable for use as a vaccine vector. In the present study, an avirulent NDV vector was generated and its potential to express CAT protein was evaluated. The CAT gene was under the control of NDV transcriptional start and stop signals and was inserted immediately before the open reading frame of the viral 3′-proximal nucleocapsid protein gene. A recombinant NDV expressing CAT activity at a high level was recovered. The replication and pathogenesis of the CAT-expressing recombinant NDV were not modified significantly. These results indicate the potential utility of an avirulent NDV as a vaccine vector.

scholarly journals A Novel Cre Recombinase-MediatedIn VivoMinicircle DNA (CRIM) Vaccine Provides Partial Protection against Newcastle Disease Virus

2019 ◽  
Vol 85 (14) ◽  
Author(s):  
Yanlong Jiang ◽  
Xing Gao ◽  
Ke Xu ◽  
Jianzhong Wang ◽  
Haibin Huang ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Vaccine Development ◽  
Cre Recombinase ◽  
Attractive Alternative ◽  
Vaccine Platform ◽  
Veterinary Vaccine ◽  
Minicircle Dna

ABSTRACTMinicircle DNA (mcDNA), which contains only the necessary components for eukaryotic expression and is thus smaller than traditional plasmids, has been designed for application in genetic manipulation. In this study, we constructed a novel plasmid containing both the Cre recombinase under the phosphoglycerate kinase (PGK) promoter and recombinantlox66andlox71sites located outside the cytomegalovirus (CMV) expression cassette. The strictly controlled synthesis of Cre recombinasein vivomaintained the complete form of the plasmidin vitro, whereas thein vivoproduction of Cre transformed the parental plasmid to mcDNA after transfection. The newly designedCrerecombinase-mediatedin vivomcDNA platform, named CRIM, significantly increased the nuclear entry of mcDNA, followed by increased production of mRNA and protein, using enhanced green fluorescent protein (EGFP) as a model. Similar results were also observed in chickens when the vaccine was delivered by the regulated-delayed-lysisSalmonellastrain χ11218, where significantly increased production of EGFP was observed in chicken livers. Then, we used the HN gene of genotype VII Newcastle disease virus as an antigen model to construct the traditional plasmid pYL43 and the novel mcDNA plasmid pYL47. After immunization, our CRIM vaccine provided significantly increased protection against challenge compared with that of the traditional plasmid, providing us with a novel mcDNA vaccine platform.IMPORTANCEMinicircle DNA (mcDNA) has been considered an attractive alternative to DNA vaccines; however, the relatively high cost and complicated process of purifying mcDNA dramatically restricts the application of mcDNA in the veterinary field. We designed a novelin vivomcDNA platform in which the complete plasmid could spontaneously transform into mcDNAin vivo. In combination with the regulated-delayed-lysisSalmonellastrain, the newly designed mcDNA vaccine provides us with an elegant platform for veterinary vaccine development.

scholarly journals Structural and functional impact of the H5 hemagglutinin expression into a NDV vector vaccine backbone

2020 ◽  
Author(s):  
Duchatel Victoria ◽  
Steensels Mieke ◽  
Verleysen Eveline ◽  
Ingrao Fiona ◽  
Mast Jan ◽  
...  
Keyword(s):  
Avian Influenza ◽  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Parental Strain ◽  
Surface Expression ◽  
Vector Vaccine ◽  
Entry Pathway ◽  
The Impact

ABSTRACTTo overcome some of the shortcomings of classical whole virus avian influenza (AI) inactivated vaccines, recombinant vector vaccines, such as recombinant Newcastle disease virus (NDV) vaccines expressing the immunogenic H5 hemagglutinin of AI (rNDV-H5), have been developed. The impact of H5 insertion and surface expression on NDV structure and functionality of a specific bivalent rNDV-H5 vaccine was investigated here.Structural analysis by immunogold labeling demonstrated the impact of the H5 expression on the surface expression of the rNDV-H5 glycoproteins resulting in a decreased and increased number of fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins, respectively, compared with the NDV LaSota parental strain. Accordingly, increased hemagglutinating and neuraminidase activities were observed for the rNDV-H5 vaccine.Functional analysis by monoclonal antibody (mAb) neutralization demonstrated H5 involvement in the rNDV-H5 entry pathway by a reduced in vitro infectivity in the presence of neutralizing H5-specific mAb and confirmed the major role of the F glycoprotein in the rNDV-H5 entry pathway as F-specific mAb neutralization resulted in a more important decrease of rNDV-H5 infectivity. However, a significantly lower impact of F-neutralization on rNDV-H5 infectivity was observed compared with the parental strain, confirming the H5-involvement in the rNDV-H5 entry.IMPORTANCETo prevent economic loss in the poultry industry, vaccination against two major treats, Newcastle Disease Virus (NDV) and Avian Influenza Virus (AIV), is one of major strategy. However, despite intense vaccination campaigns, ND continues to circulate, and AI vaccination expresses shortcomings. In consequence, bivalent vaccines improving simultaneously AI and ND protection in poultry are developed, and tested for their protective effect while their inherent characteristics are scarcely evaluated. The significance of this paper is to evaluate the impact of the H5 insertion on the NDV structure and functionality in comparison to the parental NDV vaccine, using the rNDV-H5 from Lohmann as material. This advanced characterization helps to better understand the underlying mechanisms of vaccine entry and could help improving vaccination.

scholarly journals Newcastle Disease Virus as a Vaccine Vector for 20 Years: A Focus on Maternally Derived Antibody Interference

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 222 ◽  
Author(s):  
Zenglei Hu ◽  
Jie Ni ◽  
Yongzhong Cao ◽  
Xiufan Liu
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Research Work ◽  
Vaccine Vector ◽  
The Past ◽  
Protective Antigens ◽  
Recent Advances ◽  
History Of ◽  
Remarkable Progress

It has been 20 years since Newcastle disease virus (NDV) was first used as a vector. The past two decades have witnessed remarkable progress in vaccine generation based on the NDV vector and optimization of the vector. Protective antigens of a variety of pathogens have been expressed in the NDV vector to generate novel vaccines for animals and humans, highlighting a great potential of NDV as a vaccine vector. More importantly, the research work also unveils a major problem restraining the NDV vector vaccines in poultry, i.e., the interference from maternally derived antibody (MDA). Although many efforts have been taken to overcome MDA interference, a lack of understanding of the mechanism of vaccination inhibition by MDA in poultry still hinders vaccine improvement. In this review, we outline the history of NDV as a vaccine vector by highlighting some milestones. The recent advances in the development of NDV-vectored vaccines or therapeutics for animals and humans are discussed. Particularly, we focus on the mechanisms and hypotheses of vaccination inhibition by MDA and the efforts to circumvent MDA interference with the NDV vector vaccines. Perspectives to fill the gap of understanding concerning the mechanism of MDA interference in poultry and to improve the NDV vector vaccines are also proposed.

scholarly journals Establishing a Robust Manufacturing Platform for Recombinant Veterinary Vaccines: An Adenovirus-Vector Vaccine to Control Newcastle Disease Virus Infections of Poultry in Sub-Saharan Africa

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 338 ◽  
Author(s):  
Omar Farnós ◽  
Esayas Gelaye ◽  
Khaled Trabelsi ◽  
Alice Bernier ◽  
Kumar Subramani ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Animal Health ◽  
Sub Saharan Africa ◽  
Hek293 Cells ◽  
Productive Infection ◽  
Effective Vaccine ◽  
Sub Saharan ◽  
Vectored Vaccine

Developing vaccine technology platforms to respond to pandemic threats or zoonotic diseases is a worldwide high priority. The risk of infectious diseases transmitted from wildlife and domestic animals to humans makes veterinary vaccination and animal health monitoring highly relevant for the deployment of public health global policies in the context of “one world, one health” principles. Sub-Saharan Africa is frequently impacted by outbreaks of poultry diseases such as avian influenza and Newcastle Disease (ND). Here, an adenovirus-vectored vaccine technology platform is proposed for rapid adaptation to ND or other avian viral threats in the region. Ethiopian isolates of the Newcastle Disease virus (NDV) were subjected to sequence and phylogenetic analyses, enabling the construction of antigenically matched vaccine candidates expressing the fusion (F) and hemagglutinin-neuraminidase (HN) proteins. A cost-effective vaccine production process was developed using HEK293 cells in suspension and serum-free medium. Productive infection in bioreactors (1–3 L) at 2 × 106 cells/mL resulted in consistent infectious adenoviral vector titers of approximately 5–6 × 108 TCID50/mL (approximately 1011VP/mL) in the harvest lysates. Groups of chickens were twice immunized with 1 × 1010 TCID50 of the vectors, and full protection against a lethal NDV challenge was provided by the vector expressing the F antigen. These results consolidate the basis for a streamlined and scalable-vectored vaccine manufacturing process for deployment in low- and medium-income countries.

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