scholarly journals Novel Recombinant Newcastle Disease Virus-Based In Ovo Vaccines Bypass Maternal Immunity to Provide Full Protection from Early Virulent Challenge

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1189
Author(s):  
Kiril M. Dimitrov ◽  
Tonya L. Taylor ◽  
Valerie C. Marcano ◽  
Dawn Williams-Coplin ◽  
Timothy L. Olivier ◽  
...  

Newcastle disease (ND) is one of the most economically important poultry diseases. Despite intensive efforts with current vaccination programs, this disease still occurs worldwide, causing significant mortality even in vaccinated flocks. This has been partially attributed to a gap in immunity during the post-hatch period due to the presence of maternal antibodies that negatively impact the replication of the commonly used live vaccines. In ovo vaccines have multiple advantages and present an opportunity to address this problem. Currently employed in ovo ND vaccines are recombinant herpesvirus of turkeys (HVT)-vectored vaccines expressing Newcastle disease virus (NDV) antigens. Although proven efficient, these vaccines have some limitations, such as delayed immunogenicity and the inability to administer a second HVT vaccine post-hatch. The use of live ND vaccines for in ovo vaccination is currently not applicable, as these are associated with high embryo mortality. In this study, recombinant NDV-vectored experimental vaccines containing an antisense sequence of avian interleukin 4 (IL4R) and their backbones were administered in ovo at different doses in 18-day-old commercial eggs possessing high maternal antibodies titers. The hatched birds were challenged with virulent NDV at 2 weeks-of-age. Post-hatch vaccine shedding, post-challenge survival, challenge virus shedding, and humoral immune responses were evaluated at multiple timepoints. Recombinant NDV (rNDV) vaccinated birds had significantly reduced post-hatch mortality compared with the wild-type LaSota vaccine. All rNDV vaccines were able to penetrate maternal immunity and induce a strong early humoral immune response. Further, the rNDV vaccines provided protection from clinical disease and significantly decreased virus shedding after early virulent NDV challenge at two weeks post-hatch. The post-challenge hemagglutination-inhibition antibody titers in the vaccinated groups remained comparable with the pre-challenge titers, suggesting the capacity of the studied vaccines to prevent efficient replication of the challenge virus. Post-hatch survival after vaccination with the rNDV-IL4R vaccines was dose-dependent, with an increase in survival as the dose decreased. This improved survival and the dose-dependency data suggest that novel attenuated in ovo rNDV-based vaccines that are able to penetrate maternal immunity to elicit a strong immune response as early as 14 days post-hatch, resulting in high or full protection from virulent challenge, show promise as a contributor to the control of Newcastle disease.

Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 953
Author(s):  
Valerie C. Marcano ◽  
Stivalis Cardenas-Garcia ◽  
Diego G. Diel ◽  
Luciana H. Antoniassi da Silva ◽  
Robert M. Gogal ◽  
...  

In ovo vaccination has been employed by the poultry industry for over 20 years to control numerous avian diseases. Unfortunately, in ovo live vaccines against Newcastle disease have significant limitations, including high embryo mortality and the inability to induce full protection during the first two weeks of life. In this study, a recombinant live attenuated Newcastle disease virus vaccine containing the antisense sequence of chicken interleukin 4 (IL-4), rZJ1*L-IL4R, was used. The rZJ1*L-IL4R vaccine was administered in ovo to naïve specific pathogen free embryonated chicken eggs (ECEs) and evaluated against a homologous challenge. Controls included a live attenuated recombinant genotype VII vaccine based on the virus ZJ1 (rZJ1*L) backbone, the LaSota vaccine and diluent alone. In the first of two experiments, ECEs were vaccinated at 18 days of embryonation (DOE) with either 104.5 or 103.5 50% embryo infectious dose (EID50/egg) and chickens were challenged at 21 days post-hatch (DPH). In the second experiment, 103.5 EID50/egg of each vaccine was administered at 19 DOE, and chickens were challenged at 14 DPH. Chickens vaccinated with 103.5 EID50/egg of rZJ1*L-IL4R had hatch rates comparable to the group that received diluent alone, whereas other groups had significantly lower hatch rates. All vaccinated chickens survived challenge without displaying clinical disease, had protective hemagglutination inhibition titers, and shed comparable levels of challenge virus. The recombinant rZJ1*L-IL4R vaccine yielded lower post-vaccination mortality rates compared with the other in ovo NDV live vaccine candidates as well as provided strong protection post-challenge.


Pathogens ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 145
Author(s):  
Deep Prakash Saikia ◽  
Kalpana Yadav ◽  
Dinesh C. Pathak ◽  
Narayan Ramamurthy ◽  
Ajai Lawrence D’Silva ◽  
...  

Newcastle disease (ND) and avian reovirus (ARV) infections are a serious threat to the poultry industry, which causes heavy economic losses. The mesogenic NDV strain R2B is commonly used as a booster vaccine in many Asian countries to control the disease. In this seminal work, a recombinant NDV strain R2B expressing the sigma C (σC) gene of ARV (rNDV-R2B-σC) was generated by reverse genetics, characterized in vitro and tested as a bivalent vaccine candidate in chickens. The recombinant rNDV-R2B-σC virus was attenuated as compared to the parent rNDV-R2B virus as revealed by standard pathogenicity assays. The generated vaccine candidate, rNDV-R2B-σC, could induce both humoral and cell mediated immune responses in birds and gave complete protection against virulent NDV and ARV challenges. Post-challenge virus shedding analysis revealed a drastic reduction in NDV shed, as compared to unvaccinated birds.


Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 37
Author(s):  
Vilmos Palya ◽  
Tímea Tatár-Kis ◽  
Abdel Satar A. Arafa ◽  
Balázs Felföldi ◽  
Tamás Mató ◽  
...  

The control of Newcastle disease (ND) highly relies on vaccination. Immunity provided by a ND vaccine can be characterized by measuring the level of clinical protection and reduction in challenge virus shedding. The extent of shedding depends a lot on the characteristics of vaccine used and the quality of vaccination, but influenced also by the genotype of the challenge virus. We demonstrated that vaccination of SPF chicks with recombinant herpesvirus of turkey expressing the F-gene of genotype I ND virus (rHVT-ND) provided complete clinical protection against heterologous genotype VII.1.1 ND virus strain and reduced challenge virus shedding significantly. 100% of clinical protection was achieved already by 3 weeks of age, irrespective of the challenge route (intra-muscular or intra-nasal) and vaccination blocked cloacal shedding almost completely. Interestingly, oro-nasal shedding was different in the two challenge routes: less efficiently controlled following intra-nasal than intra-muscular challenge. Differences in the shedding pattern between the two challenge routes indicate that rHVT-ND vaccine induces strong systemic immunity, that is capable to control challenge virus dissemination in the body (no cloacal shedding), even when it is a heterologous strain, but less efficiently, although highly significantly (p < 0.001) suppresses the local replication of the challenge virus in the upper respiratory mucosa and consequent oro-nasal shedding.


Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 182
Author(s):  
Helena L. Ferreira ◽  
Patti J. Miller ◽  
David L. Suarez

The efficacy of an adenovirus-vectored Newcastle disease virus (NDV) vaccine expressing the fusion (F) NDV protein (adeno-F) was evaluated against challenges with virulent heterologous and homologous NDV strains to the F protein. In a preliminary study, two different doses (low and high) of adeno-F were tested against a virulent NDV strain containing the homologous NDV F protein, CA02. In a second study, at three weeks post-vaccination, the efficacy of the high dose of adeno-F was compared to a live attenuated NDV vaccine strain (LaSota) against three antigenically distinct virulent NDV challenge strains, one homologous (CA02) and two heterologous (TZ12, EG14) to F in the vectored vaccine. In both experiments, clinical signs, mortality, virus shedding, and humoral response were evaluated. In the first experiment, the survival rates from birds vaccinated with adeno-F at a high and low dose were 100% and 25%, respectively. In the second experiment, birds vaccinated with the high dose of adeno-F had a survival rate of 80%, 75%, and 65% after challenge with the CA02, TZ12, and EG14 viruses, respectively. All of the LaSota-vaccinated birds survived post-challenge no matter the NDV challenge strain. High antibody titers were detected after vaccination with LaSota by HI and ELISA tests. The majority of adeno-F-vaccinated birds had detectable antibodies using the ELISA test, but not using the HI test, before the challenge. The data show that both the similarity of the F protein of the adeno-F vaccine to the challenge virus and the adeno-F vaccination dose affect the efficacy of an adenovirus-vectored NDV vaccine against a virulent NDV challenge.


Vaccine ◽  
2019 ◽  
Vol 37 (3) ◽  
pp. 444-451
Author(s):  
Xiaohong Xu ◽  
Zhuang Ding ◽  
Qianliang Yuan ◽  
Jiaxin Ding ◽  
Jindou Li ◽  
...  

mBio ◽  
2015 ◽  
Vol 6 (4) ◽  
Author(s):  
Sunil K. Khattar ◽  
Vinoth Manoharan ◽  
Bikash Bhattarai ◽  
Celia C. LaBranche ◽  
David C. Montefiori ◽  
...  

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.


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