Enhanced protection by recombinant newcastle disease virus expressing infectious bronchitis virus spike ectodomain and chicken granulocyte-macrophage colony-stimulating factor

Authors: KHALID, ZUBAIR - Auburn University; HE, LEI - Henan University Of Science And Technology; Yu, Qingzhong; BREEDLOVE, C - Auburn University; JOINER, K - Auburn University; TORO, HAROLDO - Auburn University

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2021
Publication Date: 5/18/2021
Citation: Khalid, Z., He, L., Yu, Q., Breedlove, C., Joiner, K., Toro, H. 2021. Enhanced protection by recombinant newcastle disease virus expressing infectious bronchitis virus spike ectodomain and chicken granulocyte-macrophage colony-stimulating factor. Avian Diseases. 65(3):364–372. https://doi.org/10.1637/aviandiseases-D-21-00032.
DOI: https://doi.org/10.1637/aviandiseases-D-21-00032

Interpretive Summary: Infectious bronchitis virus (IBV), a chicken coronavirus, remains a major cause for economic losses in the poultry industry worldwide. Vaccination with a serotype-specific attenuated live IBV vaccine is a common practice to control the disease. However, like most coronaviruses, the IBV vaccine viruses are constantly evolving in the vaccinated chickens. Some of the mutated vaccine subpopulations revert virulence or recombine with a wild-type IBV, contributing to the IB outbreaks. We previously reported that the Newcastle disease virus (NDV) recombinant LaSota strain (rLS) expressing IBV Arkansas-type (Ark) spike ectodomain (Se) provides suboptimal protection against IBV challenge. To improve the vaccine efficacy, in the present study, we developed a new recombinant NDV, rLS/ArkSe.GMCSF, expressing a chicken cytokine (GMCSF), in addition to IBV Ark Se. Vaccination of chickens with this new vaccine candidate significantly reduced viral load and tracheal lesions after challenge compared to chickens vaccinated with rLS/ArkSe. Chickens vaccinated (primed) with this new vaccine and boosted with the commonly used IBV Mass-type vaccine conferred significant cross-protection against IBV Ark-type challenge. These results suggest that rLS/GMCSF co-expressing the Se of regionally relevant IBV serotypes can be used in combination with live Mass to protect against regionally circulating IBV variant strains.

Technical Abstract: We previously reported that Newcastle disease virus (NDV) recombinant LaSota strain (rLS) expressing infectious bronchitis virus (IBV) Arkansas-type (Ark) trimeric spike ectodomain (Se) (rLS/ArkSe) provides suboptimal protection against IBV challenge. We have now developed rLS expressing chicken granulocyte-macrophage colony-stimulating factor (GMCSF) and IBV Ark Se in an attempt to enhance vaccine effectiveness. In the current study, we first compared protection conferred by vaccination with rLS/ArkSe and rLS/ArkSe.GMCSF. Vaccinated chickens were challenged with virulent Ark and protection was determined by clinical signs, viral load and tracheal histomorphometry. Results showed that co-expression of GMCSF and the Se from rLS significantly reduced tracheal viral load and tracheal lesions compared to chickens vaccinated with rLS/ArkSe. In a second experiment, we evaluated enhancement of cross-protection of a Massachusetts (Mass) attenuated vaccine by priming or boosting with rLS/ArkSe.GMCSF. Vaccinated chickens were challenged with Ark and protection was evaluated. Results show that priming or boosting with the recombinant virus significantly increased cross-protection conferred by Mass against Ark virulent challenge. Greatest reductions of viral loads in both trachea and lachrymal fluids were observed in chickens primed with rLS/ArkSe.GMCSF and boosted with Mass. Consistently, Ark Se antibody levels measured with recombinant Ark Se-protein coated ELISA plates 14 days after boost were significantly higher in these chickens. Unexpectedly, the inverse vaccination scheme, i.e. priming with Mass and boosting with the recombinant vaccine, proved somewhat less effective. We concluded that a prime and boost strategy using rLS/ArkSe.GMCSF and the world ubiquitous Mass attenuated vaccine provides enhanced cross-protection. Thus, rLS/GMCSF co-expressing the Se of regionally relevant IBV serotypes can be used in combination with live Mass to protect against regionally circulating IBV variant strains.