Limited protection conferred by recombinant Newcastle disease virus expressing infectious bronchitis spike protein

Authors: ZEGPI, R. - Auburn University; HE, LEI - Henan Institute Of Science And Technology; Yu, Qingzhong; JOINER, K. - Auburn University; VAN SANTEN, V - Auburn University; TORO, H. - Auburn University

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/18/2019
Publication Date: 4/3/2020
Citation: Zegpi, R.A., He, L., Yu, Q., Joiner, K.S., Van Santen, V.C., Toro, H. 2020. Limited protection conferred by recombinant Newcastle disease virus expressing infectious bronchitis spike protein. Avian Diseases. 64(1):53-59. https://doi.org/10.1637/0005-2086-64.1.53.
DOI: https://doi.org/10.1637/0005-2086-64.1.53

Interpretive Summary: Infectious bronchitis virus (IBV, a coronavirus) causes severe infectious bronchitis (IB) of chickens, resulting in significant economic losses to the poultry industry in the US and around the world. Vaccination with serotype-specific attenuated live IBV vaccines is a common practice to control the disease. However, like most of the coronaviruses, the IBV vaccine viruses are constantly evolving in the vaccinated chickens. Some of the mutated vaccine subpopulations revert virulence and contribute to the IB outbreaks. Therefore, there is a need to develop a safe, genetically stable, and efficacious vaccine against IB. In this study, we generated a Newcastle disease virus (NDV) LaSota vaccine-based recombinant virus expressing a secreted trimeric Spike (S) protein of Arkansas (Ark)-type IBV (rLS/IBV-Se) as a vaccine candidate. Biological assessments demonstrated that the rLS/IBV-Se virus was safe and stable. Chickens at 1 or 10 days of age were vaccinated with different doses of the vaccine, and challenged with different virulent IBV Ark strains in two experiments. The results showed that single dose vaccination provide inefficient protection against the IBV challenge. Higher single dose or a prime-boost vaccination approach conferred significant clinical protection and reduced tracheal lesions. However, neither single dose nor a prime-boost vaccination reduced the challenge virus shedding. Thus, further development of the vaccine compositions and vaccination approach is needed to improve the overall vaccine protective efficacy.

Technical Abstract: A recombinant Newcastle disease virus (NDV) LaSota (LS) expressing secreted trimeric spike (S)-ectodomain (Se) of infectious bronchitis virus (IBV) (rLS/IBV.Se) was developed, and evaluated for protection conferred against IBV challenge. The IBV S-ectodomain protein, which is S excluding the transmembrane anchor and short cytoplasmic domain of S2, expressed from recombinant LS corresponds to an Arkansas (Ark)-type IBV. In a first experiment, chickens were primed at 1-day of age or primed at 1 day of age and boosted at 14 days of age with 104 50% embryo infectious doses EID50/bird of rLS/IBV.Se and challenged with a virulent Ark strain. While single vaccination proved completely ineffective at protecting chickens against challenge, priming and boosting reduced clinical signs and tracheal lesions but did not reduce viral load in lachrymal fluids. In experiment 2, the vaccine dose was increased to 107 EID50/bird and a different virulent Ark strain was used for challenge. In addition, chickens were singly immunized on either day 1 or day 10 after hatch. NDV antibody levels detected in vaccinated chickens were moderate with hemagglutination inhibition titers varying between 4 and 5 log2. Slightly higher antibody levels to NDV were observed in chickens vaccinated on day 10 versus day 1 but without the difference achieving statistical significance. In contrast, antibody responses using recombinant IBV S1 protein-coated ELISA plates were significantly greater in chickens vaccinated on day 10 compared to day 1. The use of a higher rLS/IBV.Se dose proved to enhance the success of single vaccination substantially compared to experiment 1. Signs and tracheal lesions were reduced more effectively in chickens vaccinated at day 10 after hatch. However, as in experiment 1, vaccination did not reduce the viral loads in tear fluids of challenged chickens. Similar results, in which no reduction in viral load in the trachea was apparent from rLS/IBV.S vaccination, have been obtained by others. Further work is needed to understand the immune responses induced by this recombinant virus that seems to provide some protection against the disease but does not reduce viral loads in the upper respiratory tract.