scholarly journals Newcastle disease virus (NDV) expressing the spike protein of SARS-CoV-2 as vaccine candidate

2020 ◽  
Author(s):  
Weina Sun ◽  
Sarah R. Leist ◽  
Stephen McCroskery ◽  
Yonghong Liu ◽  
Stefan Slamanig ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Viral Vectors ◽  
Viral Vector ◽  
Spike Protein ◽  
S Protein ◽  
Vector Vaccine ◽  
Chicken Eggs ◽  
Embryonated Chicken

AbstractDue to the lack of protective immunity of humans towards the newly emerged SARS-CoV-2, this virus has caused a massive pandemic across the world resulting in hundreds of thousands of deaths. Thus, a vaccine is urgently needed to contain the spread of the virus. Here, we describe Newcastle disease virus (NDV) vector vaccines expressing the spike protein of SARS-CoV-2 in its wild type or a pre-fusion membrane anchored format. All described NDV vector vaccines grow to high titers in embryonated chicken eggs. In a proof of principle mouse study, we report that the NDV vector vaccines elicit high levels of antibodies that are neutralizing when the vaccine is given intramuscularly. Importantly, these COVID-19 vaccine candidates protect mice from a mouse-adapted SARS-CoV-2 challenge with no detectable viral titer and viral antigen in the lungs.Research in contextEvidence before this studyThe spike (S) protein of the SARS-CoV-2 is the major antigen that notably induces neutralizing antibodies to block viral entry. Many COVID-19 vaccines are under development, among them viral vectors expressing the S protein of SARS-CoV-2 exhibit many benefits. Viral vector vaccines have the potential of being used as both live or inactivated vaccines and they can induce Th1 and Th2-based immune responses following different immunization regimens. Additionally, viral vector vaccines can be handled under BSL-2 conditions and they grow to high titers in cell cultures or other species restricted-hosts. For a SARS-CoV-2 vaccine, several viral vectors are being tested, such as adenovirus, measles virus and Modified vaccinia Ankara.Added value of this studyThe NDV vector vaccine against SARS-CoV-2 described in this study has advantages similar to those of other viral vector vaccines. But the NDV vector can be amplified in embryonated chicken eggs, which allows for high yields and low costs per dose. Also, the NDV vector is not a human pathogen, therefore the delivery of the foreign antigen would not be compromised by any pre-existing immunity in humans. Finally, NDV has a very good safety record in humans, as it has been used in many oncolytic virus trials. This study provides an important option for a cost-effective SARS-CoV-2 vaccine.Implications of all the available evidenceThis study informs of the value of a viral vector vaccine against SARS-CoV-2. Specifically, for this NDV based SARS-CoV-2 vaccine, the existing egg-based influenza virus vaccine manufactures in the U.S. and worldwide would have the capacity to rapidly produce hundreds of millions of doses to mitigate the consequences of the ongoing COVID-19 pandemic.

scholarly journals Newcastle Disease Virus V Protein Is a Determinant of Host Range Restriction

2003 ◽  
Vol 77 (17) ◽  
pp. 9522-9532 ◽  
Author(s):  
Man-Seong Park ◽  
Adolfo García-Sastre ◽  
Jerome F. Cros ◽  
Christopher F. Basler ◽  
Peter Palese
Keyword(s):  
Newcastle Disease Virus ◽  
Host Range ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Range Restriction ◽  
V Protein ◽  
Species Specific ◽  
Chicken Eggs ◽  
Host Range Restriction ◽  
Embryonated Chicken

ABSTRACT It has been demonstrated that the V protein of Newcastle disease virus (NDV) functions as an alpha/beta interferon (IFN-α/β) antagonist (M. S. Park, M. L. Shaw, J. Muñoz-Jordan, J. F. Cros, T. Nakaya, N. Bouvier, P. Palese, A. García-Sastre, and C. F. Basler, J. Virol. 77:1501-1511, 2003). We now show that the NDV V protein plays an important role in host range restriction. In order to study V functions in vivo, recombinant NDV (rNDV) mutants, defective in the expression of the V protein, were generated. These rNDV mutants grow poorly in both embryonated chicken eggs and chicken embryo fibroblasts (CEFs) compared to the wild-type (wt) rNDV. However, insertion of the NS1 gene of influenza virus A/PR8/34 into the NDV V(−) genome [rNDV V(−)/NS1] restores impaired growth to wt levels in embryonated chicken eggs and CEFs. These data indicate that for viruses infecting avian cells, the NDV V protein and the influenza NS1 protein are functionally interchangeable, even though there are no sequence similarities between the two proteins. Interestingly, in human cells, the titer of wt rNDV is 10 times lower than that of rNDV V(−)/NS1. Correspondingly, the level of IFN secreted by human cells infected with wt rNDV is much higher than that secreted by cells infected with the NS1-expressing rNDV. This suggests that the IFN antagonist activity of the NDV V protein is species specific. Finally, the NDV V protein plays an important role in preventing apoptosis in a species-specific manner. The rNDV defective in V induces apoptotic cell death more rapidly in CEFs than does wt rNDV. Taken together, these data suggest that the host range of NDV is limited by the ability of its V protein to efficiently prevent innate host defenses, such as the IFN response and apoptosis.

scholarly journals Pathological Lesions in Chicken Embryo Caused by Newly Virulent Isolate of Newcastle Disease Virus (LESI PATOLOGIS PADA EMBRIO AYAM YANG DISEBABKAN ISOLAT VIRUS PENYAKIT TETELO TERBARU YANG VIRULEN)

2019 ◽  
Vol 20 (3) ◽  
pp. 337
Author(s):  
I Gede Hendra Prasetya Wicaksana ◽  
Anak Agung Ayu Mirah Adi ◽  
I Made Kardena
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Viral Disease ◽  
Economic Losses ◽  
Valuable Insight ◽  
Virulent Isolate ◽  
Hematoxylin And Eosin ◽  
Chicken Eggs ◽  
Embryonated Chicken

Newcastle disease is a pathogenic viral disease in poultry which is infectious and can cause massive economic losses. The disease is still endemic in Indonesia. To understand the pathogenesis and the distribution pattern of the virus in the tissues, pathological observation was evaluated using newly virulent isolate Newcastle disease virus (NDV) that was inoculated in embryonated chicken eggs. As many as seven embryonic chicken eggs aged 11 days and specific antibody negative against Newcastle disease, divided into two categories: inoculated with phosphate buffer saline and inoculated with isolates. Then the allantois fluid was tested using hemagglutination assay and hemagglutination inhibition tests to prove the infection serologically. The hearts, lungs, livers and small intestines of the inoculated products were collected and followed with the process of histopathological preparation using Hematoxylin and Eosin (HE) stain. The pathological analysis showed that all organs had necrosis, hemorrhages, inflammation, and congestion. Congestion and hemorrhages in the hearts only occurred at 60% of the samples. However, necrosis, hemorrhages, and inflammation that were observed in liver occurred at 60%, 40% and 60% of the samples, respectively. Furthermore, the hearts were edema, thinner in the heart muscle fibers; while in the lungs, proliferation of pneumocyte type II was founded. Our finding provided valuable insight into the pathology of a virulent isolate of NDV which is dominated by blood circulation disorders with necrosis and inflammation in the chicken’s embryos and have important implication for the future studies.

scholarly journals Safety and Immunogenicity Analysis of a Newcastle Disease Virus (NDV-HXP-S) Expressing the Spike Protein of SARS-CoV-2 in Sprague Dawley Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Johnstone Tcheou ◽  
Ariel Raskin ◽  
Gagandeep Singh ◽  
Hisaaki Kawabata ◽  
Dominika Bielak ◽  
...  
Keyword(s):  
Newcastle Disease Virus ◽  
Disease Virus ◽  
Newcastle Disease ◽  
Second Generation ◽  
The United States ◽  
Spike Protein ◽  
High Antibody ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Antibody Titers

Despite global vaccination efforts, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve and spread globally. Relatively high vaccination rates have been achieved in most regions of the United States and several countries worldwide. However, access to vaccines in low- and mid-income countries (LMICs) is still suboptimal. Second generation vaccines that are universally affordable and induce systemic and mucosal immunity are needed. Here we performed an extended safety and immunogenicity analysis of a second-generation SARS-CoV-2 vaccine consisting of a live Newcastle disease virus vector expressing a pre-fusion stabilized version of the spike protein (NDV-HXP-S) administered intranasally (IN), intramuscularly (IM), or IN followed by IM in Sprague Dawley rats. Local reactogenicity, systemic toxicity, and post-mortem histopathology were assessed after the vaccine administration, with no indication of severe local or systemic reactions. Immunogenicity studies showed that the three vaccination regimens tested elicited high antibody titers against the wild type SARS-CoV-2 spike protein and the NDV vector. Moreover, high antibody titers were induced against the spike of B.1.1.7 (alpha), B.1.351 (beta) and B.1.617.2 (delta) variants of concern (VOCs). Importantly, robust levels of serum antibodies with neutralizing activity against the authentic SARS-CoV-2 USA‐WA1/2020 isolate were detected after the boost. Overall, our study expands the pre-clinical safety and immunogenicity characterization of NDV-HXP-S and reinforces previous findings in other animal models about its high immunogenicity. Clinical testing of this vaccination approach is ongoing in different countries including Thailand, Vietnam, Brazil and Mexico.

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