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

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 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.

Current situation and future direction of Newcastle disease vaccines

“…These findings suggest that IFN-γ may act as an antiviral factor and has no augmenting effect on virus immunogenicity. Interestingly, two independent studies revealed a robust function of an antisense IL-4 gene in regulating NDV immunogenicity [ 111 , 112 ]. Collectively, the data from these two works indicated that in ovo immunization with attenuated NDVs carrying an antisense IL-4 gene induced an early antibody response and high protection in commercial chicken eggs with high MDA titres.…”

Review detection of Newcastle disease virus

“…According to reports, there have been at least four major outbreaks of ND around the world, which have caused great harm to international trade, and each epidemic had its specific genotype ( 2 ). Despite the wide use of ND vaccination programs in the poultry industry, different wild strains of the immunized flock are still isolated ( 3 ). Simultaneously, the emergence of atypical clinical symptoms and new strains has posed many difficulties in diagnosis, prevention, and control of the disease.…”

Development of immune response against H9N2 avian influenza after vaccination

“…For example, the modified NDV expressed the hemagglutinin-neuraminidase (HN) and fusion (F) genes from a different avian paramyxovirus, such as avian paramyxovirus type 8 (Steglich et al 2013) or avian paramyxovirus type 2 (Kim, Paldurai andSamal 2017, Liu et al 2018) can overcome NDV-specific MDAs interference. In addition, recombinant NDV-vectored experimental vaccine containing an antisense sequence of avian interleukin 4 (IL4R) and their backbones is able to overcome MDAs interference by administering in ovo at 18-day-old commercial eggs (Dimitrov et al 2021). During the last few years, replicationdefective human adenoviruses serotype-5 (hAdVs-5) has emerged as an attractive vector for the development of vaccines to overcome MDAs interference in poultry.…”