Newcastle disease virus vectored infectious laryngotracheitis vaccines protect commercial broiler chickens in the presence of maternally derived antibodies
Introduction
Infectious laryngotracheitis (ILT) is an acute upper respiratory tract disease of chickens caused by the alphaherpesvirus infectious laryngotracheitis virus (ILTV) or gallid herpesvirus type 1 (GaHV-1). Despite the extensive use of attenuated, and more recently recombinant vaccines, ILT continues to affect poultry on a worldwide basis [1]. Historically, the commonly used live ILT vaccines were first attenuated in the 1950s by either multiple passages in embryonated eggs (chicken embryo origin [CEO]) or in tissue culture (tissue culture origin [TCO]) [2], [3]. Although these vaccines protect against clinical disease, they have residual virulence, which is exacerbated by continued infections of naïve birds from productively infected animals and latent carriers [4], [5], [6]. In high-density poultry rearing facilities there is a continuous reservoir of ILT viruses, both virulent and vaccinal. It has been reported that CEO vaccinal “revertants” can become the dominant field strains in poultry populations and cause outbreaks [7], [8]. Although the recombinant vaccines, turkey herpesvirus (HVT) and fowlpox virus (FPV) expressing ILTV antigens are safe [9], [10], [11], [12], [13], [14], they only induce partial protection when compared with that induced by live-attenuated vaccines [15]. Thus, a significant need exists to revise the ILT control strategies particularly regarding the development of next generation vaccines that are safe, protective and incapable of vaccinal reversion.
Recently, we developed Newcastle disease virus (NDV) recombinants expressing the ILTV glycoproteins B and D as bivalent vaccines [16]. Vaccination of one-day-old specific pathogen free (SPF) and 3-week-old commercial boiler chickens conferred complete clinical protection against virulent ILTV and NDV challenges [16]. However, there was a general concern that the maternally derived antibodies (MDA) may interfere with the immunoresponses of the chicks to the corresponding vaccines [17], [18], [19]. It has been reported that the NDV MDA confers protection to young chicks against ND, but it can also interfere with NDV vaccine efficacy at 1 day of age (DOA) [17], [19]. This interference is dependent on the titer of maternal antibodies and the strain of the NDV vaccine administered [20], [21]. The LaSota vaccine strain has been demonstrated to overcome MDA interference better than the Hitchner, B1 or V4 strains [21]. Higher levels of circulating maternal antibodies to the LaSota strain were required to depress the immunoresponse than that required to do the same for the other three strains [21]. In contrast, maternal antibodies to ILTV do not confer protection against disease nor interfere with the immune response following vaccination [22].
To evaluate whether maternal antibodies interfere with protection induced by the LaSota strain-vectored ILTV recombinants, rLS/ILTV-gB and rLS/ILTV-gD, we carried out vaccination/challenge experiments with one-day-old commercial broiler chickens that had a mean NDV MDA HI titer of 6.4 (log2) and detectable ILTV virus neutralization (VN) antibodies. The immunoresponses following vaccination and protection indices (e.g. clinical signs, body weight gain and virus shedding after ILTV challenge) suggest significant protection against ILTV challenge even in the presence of maternally derived antibodies specific for NDV and ILTV.
Section snippets
Vaccines, viruses and cells
The generation of NDV LaSota strain-vectored ILTV vaccine candidates, rLS/ILTV-gD and rLS/ILTV-gB, were previously described [16] and propagated in 9-day-old SPF chicken embryos at passage level 3. The titers of these vaccine stocks were determined by the 50% egg infective dose (EID50) assay in 9-day-old SPF chicken embryos [23]. The commercial ILTV vaccines, Vectormune (FP-LT) and Trachivax (CEO), were purchased from Ceva Biomune (Lenexa, KS) and Merck Animal Health (Summit, NJ), respectively.
Detection of MDA and immunoresponses following vaccination
To determine the titers of NDV- and ILTV-specific maternally derived antibodies in commercial broiler chickens and immunoresponses following vaccination, serum samples collected at 1 DOA (before vaccination) and at 10 and 21 DOA (before challenge) were subjected to the HI (for NDV antibodies) and VN (for ILTV antibodies) tests. These results (Table 1) showed that unvaccinated birds at 1 DOA possessed a mean NDV HI titer of 6.4 (log2) and a mean ILTV VN titer of 0.51 (log10). The NDV HI titer
Discussion
In this study, we evaluated the protective efficacies of two NDV LaSota strain-vectored ILTV vaccine candidates rLS/ILTV-gB or rLS/ILTV-gD in commercial maternal antibody positive broiler chickens. The results showed that both bivalent vaccine candidates conferred clinical protection, maintained body-weight gains, and significantly reduced ILTV load following challenge. The data suggest that the presence of maternally derived antibodies capable of neutralizing ILTV and high titers of NDV MDA
Conflict of interest
The authors declare that they have no conflicts of interest.
Acknowledgements
The authors wish to thank Xiuqin Xia, Teresa Ross, Fenglan Li, and Sylva Riblet for excellent technical assistance. This research was supported by United States Department of Agriculture, ARS CRIS project 6040-32000-067-00D. W. Zhao and Z. Zhang were sponsored by a scholarship from China Scholarship Council, China, Y. Li was sponsored by a scholarship from Shandong Academy of Agricultural Sciences, China, J. Yang was sponsored by a scholarship from Chongqing Academy of Agricultural Sciences,
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Current status of virus-vectored vaccines against pathogens that affect poultry
2020, VaccineCitation Excerpt :The use of rNDV as experimental vaccines for poultry has been assessed during the last fifteen years. Thus, NDV-based viral vectors expressing of the IBDV VP2 protein [88;89], ILTV gB, gD and gC glycoproteins [90;91], IBV S gene [92;93] and influenza NA and HA glycoproteins [94;95;96;97;98], have been obtained and evaluated as immunogens for chickens. Besides, rNDV expressing the glycoprotein G of avian metapneumovirus and the VP3 protein of goose parvovirus [99;100] have also been reported as experimental vaccines for turkeys and goslings, respectively (see Table 2 for details).
Evaluation of immune efficacy of recombinant PRRSV vectored vaccine rPRRSV-E2 in piglets with maternal derived antibodies
2020, Veterinary MicrobiologyCitation Excerpt :However, high level of MDA can also interfere with vaccination and making some vaccines partially or completely ineffective after immunization, resulting in immune failure (Pastoret, 2007; Siegrist, 2007). It has been reported that the degree of MDA interference on vaccinal efficacy depended on MDA titers and the genotype of the vaccine strain (Yu et al., 2017) For innovation of live viral vectored vaccine, it is inevitable that the MDA interferes must be considered in vaccine immunization, especially the MDA against the viral vector.
Genetic stability of a Newcastle disease virus vectored infectious laryngotracheitis virus vaccine after serial passages in chicken embryos
2020, VaccineCitation Excerpt :These “revertants” have become the dominant field strains in poultry populations and are the cause of field ILT outbreaks [11,12]. To overcome these problems associated with live attenuated ILTV vaccine strains, we have developed an NDV LaSota vaccine strain-based recombinant virus expressing the ILTV gD protein as a bivalent vaccine and demonstrated that vaccination of chickens with the recombinant vaccine, rLS/ILTV-gD, confers complete protection against virulent NDV challenge and significant protection against pathogenic ILTV challenge [13,14]. NDV contains a non-segmented, single-stranded negative-sense RNA genome of approximately 15 kb in length, which consists of six genes flanked by a 3′ Leader and 5′ Trailer in the order 3′- nucleocapsid protein (NP)-phosphoprotein (P)-matrix protein (M)-fusion protein (F)-hemagglutinin-neuraminidase (HN)-large polymerase (L)-5′ [15–17].
- 1
Present address: Shandong Poultry Research Institute, Jinan 250023, China.
- 2
Present address: Chongqing Academy of Animal Sciences, Chongqing 402460, China.
- 3
Present address: Beijing Centre for Disease Control and Prevention, Beijing 100013, China.
- 4
Present address: College of Life Sciences, Northeast Agricultural University, Harbin 150030, China.
- 5
Present address: Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan 430070, China.