Novel recombinant Newcastle disease virus-based in Ovo vaccines bypass maternal immunity to provide full protection from early virulent challenge

Authors: DIMITROV, KIRIL - Consultant; Taylor, Tonya; Marcano, Valerie; Williams Coplin, Tina; Olivier, Timothy; Yu, Qingzhong; GOGAL JR., ROBERT - University Of Georgia; Suarez, David; Afonso, Claudio

Submitted to: Vaccines
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2021
Publication Date: 10/15/2021
Citation: Dimitrov, K.M., Taylor, T.L., Marcano, V.C., Williams Coplin, T.D., Olivier, T.L., Yu, Q., Gogal Jr., R.M., Suarez, D.L., Afonso, C.L. 2021. Novel recombinant Newcastle disease virus-based in Ovo vaccines bypass maternal immunity to provide full protection from early virulent challenge. Vaccines. 9(10):1189. https://doi.org/10.3390/vaccines9101189.
DOI: https://doi.org/10.3390/vaccines9101189

Interpretive Summary: Newcastle disease (ND) outbreaks are a global challenge to the poultry industry. The disease is controlled through biosecurity and vaccination. However, outbreaks of ND occur worldwide, even in vaccinated flocks. Live vaccines are administered through vaccination programs as early as day-old chickens but the presence of antibody from the hen in the egg yolk, maternal immunity, often negatively affects development of a strong immune response. This requires additional booster vaccinations leaving a window during which birds are sub-optimally protected. Inactivated vaccines are less affected by the presence of maternal immunity, but they do not elicit mucosal immunity. In ovo vaccines, vaccines administered while the chicken is still inside the egg, against ND using the herpes virus of turkeys as a vector have been developed, but they have the limitations of inducing a delayed immune response 3-4 weeks, leaving a gap in immunity between the decrease of maternal antibodies and reaching sufficient protection. These limitations suggest the development of alternative approaches for vaccine generation is probably needed. In ovo vaccines used 2-3 days before hatch present an interesting opportunity. However, use of live ND vaccines in ovo has resulted in very high mortality of the embryos and chicks post-hatch. In this study, two recombinant NDV-vectored vaccines were tested in ovo in 18-day-old commercial eggs with a high level of maternal antibodies. The hatched birds were challenged with virulent NDV early after hatch - at two weeks of age. The studied vaccines had low post-hatch mortality, efficiently overcame maternal immunity, and induced a strong immune response. The tested vaccines provided full protection from early challenge with virulent NDV. The post-challenge levels of antibodies in the vaccinated birds did not increase compared to pre-challenge, suggesting that the studied vaccines efficiently suppress replication of the challenge virus. Our results demonstrate the development of vaccines able to overcome maternal immunity, elicit a strong immune response by two weeks post-hatch (the time when level of maternal antibodies decrease), and provide full protection from virulent challenge. These vaccines are good candidates for further testing with lower doses and additional attenuation through reverse genetics.

Technical 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.