Vaccines

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19 pages, 3570 KiB

Open AccessArticle

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

by Kiril M. Dimitrov, Tonya L. Taylor, Valerie C. Marcano, Dawn Williams-Coplin, Timothy L. Olivier, Qingzhong Yu, Robert M. Gogal, Jr., David L. Suarez and Claudio L. Afonso

Vaccines 2021, 9(10), 1189; https://doi.org/10.3390/vaccines9101189 - 15 Oct 2021

Cited by 5 | Viewed by 3562

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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17 pages, 1568 KiB

Open AccessFeature PaperArticle

A Novel Recombinant Newcastle Disease Vaccine Improves Post- In Ovo Vaccination Survival with Sustained Protection against Virulent Challenge

by Valerie C. Marcano, Stivalis Cardenas-Garcia, Diego G. Diel, Luciana H. Antoniassi da Silva, Robert M. Gogal, Jr., Patti J. Miller, Corrie C. Brown, Salman Latif Butt, Iryna V. Goraichuk, Kiril M. Dimitrov, Tonya L. Taylor, Dawn Williams-Coplin, Timothy L. Olivier, James B. Stanton and Claudio L. Afonso

Vaccines 2021, 9(9), 953; https://doi.org/10.3390/vaccines9090953 - 26 Aug 2021

Cited by 5 | Viewed by 4364

Abstract

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 [...] Read more.

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 10^4.5 or 10^3.5 50% embryo infectious dose (EID₅₀/egg) and chickens were challenged at 21 days post-hatch (DPH). In the second experiment, 10^3.5 EID₅₀/egg of each vaccine was administered at 19 DOE, and chickens were challenged at 14 DPH. Chickens vaccinated with 10^3.5 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. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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15 pages, 12244 KiB

Open AccessFeature PaperArticle

Activation of Cytotoxic Lymphocytes and Presence of Regulatory T Cells in the Trachea of Non-Vaccinated and Vaccinated Chickens as a Recall to an Infectious Laryngotracheitis Virus (ILTV) Challenge

by Daniel Maekawa, Sylva M. Riblet, Patrick Whang, David J. Hurley and Maricarmen Garcia

Vaccines 2021, 9(8), 865; https://doi.org/10.3390/vaccines9080865 - 5 Aug 2021

Cited by 10 | Viewed by 2706

Abstract

While the protective efficacy of the infectious laryngotracheitis virus (ILTV) vaccines is well established, little is known about which components of the immune response are associated with effective resistance and vaccine protection. Early studies have pointed to the importance of the T cell-mediated [...] Read more.

While the protective efficacy of the infectious laryngotracheitis virus (ILTV) vaccines is well established, little is known about which components of the immune response are associated with effective resistance and vaccine protection. Early studies have pointed to the importance of the T cell-mediated immune responses. This study aimed to evaluate the activation of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells and to quantify the presence of regulatory T cells (Tregs) in the larynx–trachea of chickens vaccinated with chicken embryo origin (CEO), tissue culture origin (TCO) and recombinant Herpesvirus of Turkey-laryngotracheitis (rHVT-LT) vaccines after challenge. Our results indicated that CEO vaccine protection was characterized by early CTLs and activated CTLs enhanced responses. TCO and rHVT-LT protection were associated with a moderate increase in resting and activated CTLs followed by an enhanced NK cell response. Tregs increase was only detected in the non-vaccinated challenged group, probably to support healing of the severe trachea epithelial damage. Taken together, our results revealed main differences in the cellular immune responses elicited by CEO, TCO, and rHVT-LT vaccination in the upper respiratory tract after challenge, and that activated CTLs rather than NK cells play a main role in vaccine protection. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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18 pages, 2767 KiB

Open AccessArticle

Protection against Different Genotypes of Newcastle Disease Viruses (NDV) Afforded by an Adenovirus-Vectored Fusion Protein and Live NDV Vaccines in Chickens

by Helena L. Ferreira, Patti J. Miller and David L. Suarez

Vaccines 2021, 9(2), 182; https://doi.org/10.3390/vaccines9020182 - 21 Feb 2021

Cited by 9 | Viewed by 4037

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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15 pages, 2137 KiB

Open AccessArticle

A Novel Effective and Safe Vaccine for Prevention of Marek’s Disease Caused by Infection with a Very Virulent Plus (vv+) Marek’s Disease Virus

by Yifei Liao, Sanjay M. Reddy, Owais A. Khan, Aijun Sun and Blanca Lupiani

Vaccines 2021, 9(2), 159; https://doi.org/10.3390/vaccines9020159 - 16 Feb 2021

Cited by 11 | Viewed by 4024

Abstract

Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset lymphoma in chickens. Marek’s disease (MD) is effectively controlled using vaccination; however, MDV continues to break through vaccinal immunity, due to the emergence of highly virulent field strains. Earlier studies [...] Read more.

Marek’s disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset lymphoma in chickens. Marek’s disease (MD) is effectively controlled using vaccination; however, MDV continues to break through vaccinal immunity, due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV resulted in an attenuated virus that protects against MD in chickens challenged with highly virulent field strains. However, the meq deleted virus retains the ability to induce significant lymphoid organ atrophy. In a different study, we found that the deletion of the vIL8 gene resulted in the loss of lymphoid organ atrophy in inoculated chickens. Here, we describe the generation of a recombinant MDV from which both meq and vIL8 genes were deleted. In vitro studies revealed that the meq and vIL8 double deletion virus replicated at levels similar to the parental very virulent plus (vv+) virus. In addition, in vivo studies showed that the double deletion mutant virus (686BAC-ΔMeqΔvIL8) conferred protection comparable to CVI988, a commercial vaccine strain, when challenged with a vv+ MDV virus, and significantly reduced lymphoid organ atrophy, when compared to meq null virus, in chickens. In conclusion, our study describes the development of a safe and effective vaccine candidate for prevention of MD in chickens. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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12 pages, 4168 KiB

Open AccessArticle

Development of a Viral-Like Particle Candidate Vaccine Against Novel Variant Infectious Bursal Disease Virus

by Yulong Wang, Nan Jiang, Linjin Fan, Li Gao, Kai Li, Yulong Gao, Xinxin Niu, Wenying Zhang, Hongyu Cui, Aijing Liu, Qing Pan, Changjun Liu, Yanping Zhang, Xiaomei Wang and Xiaole Qi

Vaccines 2021, 9(2), 142; https://doi.org/10.3390/vaccines9020142 - 10 Feb 2021

Cited by 10 | Viewed by 3375

Abstract

Infectious bursal disease (IBD), an immunosuppressive disease of young chickens, is caused by infectious bursal disease virus (IBDV). Novel variant IBDV (nVarIBDV), a virus that can evade immune protection against very virulent IBDV (vvIBDV), is becoming a threat to the poultry industry. Therefore, [...] Read more.

Infectious bursal disease (IBD), an immunosuppressive disease of young chickens, is caused by infectious bursal disease virus (IBDV). Novel variant IBDV (nVarIBDV), a virus that can evade immune protection against very virulent IBDV (vvIBDV), is becoming a threat to the poultry industry. Therefore, nVarIBDV-specific vaccine is much needed for nVarIBDV control. In this study, the VP2 protein of SHG19 (a representative strain of nVarIBDV) was successfully expressed using an Escherichia coli expression system and further purified via ammonium sulfate precipitation and size-exclusion chromatography. The purified protein SHG19-VP2-466 could self-assemble into 25-nm virus-like particle (VLP). Subsequently, the immunogenicity and protective effect of the SHG19-VLP vaccine were evaluated using animal experiments, which indicated that the SHG19-VLP vaccine elicited neutralization antibodies and provided 100% protection against the nVarIBDV. Furthermore, the protective efficacy of the SHG19-VLP vaccine against the vvIBDV was evaluated. Although the SHG19-VLP vaccine induced a comparatively lower vvIBDV-specific neutralization antibody titer, it provided good protection against the lethal vvIBDV. In summary, the SHG19-VLP candidate vaccine could provide complete immune protection against the homologous nVarIBDV as well as the heterologous vvIBDV. This study is of significance to the comprehensive prevention and control of the recent atypical IBD epidemic. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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15 pages, 1806 KiB

Open AccessArticle

A Herpesvirus of Turkey-Based Vector Vaccine Reduces Transmission of Newcastle Disease Virus in Commercial Broiler Chickens with Maternally Derived Antibodies

by Timea Tatár-Kis, Egil A.J. Fischer, Christophe Cazaban, Edit Walkó-Kovács, Zalan G. Homonnay, Francisca C. Velkers, Vilmos Palya and J. Arjan Stegeman

Vaccines 2020, 8(4), 614; https://doi.org/10.3390/vaccines8040614 - 16 Oct 2020

Cited by 10 | Viewed by 4701

Abstract

Newcastle Disease is one of the most important infectious poultry diseases worldwide and is associated with high morbidity, mortality, and economic loss. In several countries, vaccination is applied to prevent and control outbreaks; however, information on the ability of vaccines to reduce transmission [...] Read more.

Newcastle Disease is one of the most important infectious poultry diseases worldwide and is associated with high morbidity, mortality, and economic loss. In several countries, vaccination is applied to prevent and control outbreaks; however, information on the ability of vaccines to reduce transmission of ND virus (NDV) is sparse. Here we quantified the transmission of velogenic NDV among 42-day-old broilers. Chickens were either vaccinated with a single dose of a vector vaccine expressing the F protein (rHVT-ND) at day-old in the presence of maternally derived antibodies or kept unvaccinated. Seeders were challenged 8 h before the co-mingling with the corresponding contacts from the same group. Infection was monitored by daily testing of cloacal and oro-nasal swabs with reverse transcription-real-time PCR and by serology. Vaccinated birds were completely protected against clinical disease and virus excretion was significantly reduced compared to the unvaccinated controls that all died during the experiment. The reproduction ratio, which is the average number of secondary infections caused by an infectious bird, was significantly lower in the vaccinated group (0.82 (95% CI 0.38–1.75)) than in the unvaccinated group (3.2 (95% CI 2.06–4.96)). Results of this study demonstrate the potential of rHVT-ND vaccine in prevention and control of ND outbreaks. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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12 pages, 1706 KiB

Open AccessArticle

Depletion of CD8αβ⁺ T Cells in Chickens Demonstrates Their Involvement in Protective Immunity towards Marek’s Disease with Respect to Tumor Incidence and Vaccinal Protection

by Supawadee Umthong, John R. Dunn and Hans H. Cheng

Vaccines 2020, 8(4), 557; https://doi.org/10.3390/vaccines8040557 - 24 Sep 2020

Cited by 9 | Viewed by 3121

Abstract

Marek’s disease (MD) is a lymphoproliferative disease in chickens caused by Marek’s disease virus (MDV), a highly oncogenic alphaherpesvirus. Since 1970, MD has been controlled through widespread vaccination of commercial flocks. However, repeated and unpredictable MD outbreaks continue to occur in vaccinated flocks, [...] Read more.

Marek’s disease (MD) is a lymphoproliferative disease in chickens caused by Marek’s disease virus (MDV), a highly oncogenic alphaherpesvirus. Since 1970, MD has been controlled through widespread vaccination of commercial flocks. However, repeated and unpredictable MD outbreaks continue to occur in vaccinated flocks, indicating the need for a better understanding of MDV pathogenesis to guide improved or alternative control measures. As MDV is an intracellular pathogen that infects and transforms CD4+ T cells, the host cell-mediated immune response is considered to be vital for controlling MDV replication and tumor formation. In this study, we addressed the role of CD8+ T cells in vaccinal protection by widely-used monovalent (SB-1 and HVT) and bivalent (SB-1+HVT) MD vaccines. We established a method to deplete CD8+ T cells in chickens and found that their depletion through injection of anti-CD8 monoclonal antibodies (mAb) increased tumor induction and MD pathology, and reduced vaccinal protection to MD, which supports the important role of CD8+ T cells for both MD and vaccinal protection. Full article

(This article belongs to the Special Issue Vaccine Research against Significant Viral Diseases of Poultry)

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