A Single Vaccination of IBDV Subviral Particles Generated by Kluyveromyces marxianus Efficiently Protects Chickens against Novel Variant and Classical IBDV Strains

Abstract

Infectious bursal disease (IBD), caused by the infectious bursal disease virus (IBDV), is a highly contagious and immunosuppressive disease in chickens worldwide. The novel variant IBDV (nvIBDV) has been emerging in Chinese chicken farms since 2017, but there are no available vaccines that can provide effective protection. Herein, the capsid protein VP2 from nvIBDV strain FJ-18 was expressed in Kluyveromyces marxianus with the aim to produce nvIBDV subviral particles (SVPs). Two recombinant strains constructed for expression of nvIBDV VP2 (nvVP2) and His-tagged VP2 (nvHVP2) formed two types of nvIBDV subviral particles (SVPs), namely nvVP2-SVPs and nvHVP2-SVPs. TEM scans showed that both SVPs were about 25 nm in diameter, but there was a large portion of nvVP2-SVPs showing non-spherical particles. Molecular dynamics simulations indicate that an N-terminal His tag strengthened the interaction of the nvHVP2 monomer and contributed to the assembly of SVPs. Vaccination of chicks with the nvHVP2-SVPs provided 100% protection against novel variant IBDV infection when challenged with the FJ-18 strain, as well as the classical strain BC6/85. By contrast, vaccination with the nvVP2-SVPs only provided 60% protection against their parent FJ-18 strain, suggesting that the stable conformation of subviral particles posed a great impact on their protective efficacy. Our results showed that the nvHVP2-SVPs produced by the recombinant K. marxianus strain is an ideal vaccine candidate for IBDV eradication.

Fluorescence lifetime imaging of NAD(P)H upon oxidative stress in Kluyveromyces marxianus

“…The K. marxianus strain FIM-1 (Wu et al, 2020), and the S. cerevisiae strain S288C (Yu et al, 2021), were used in this study. K. marxianus strains KML and KMH were derived from KM-HPV2, which expressed IBDV-VP2 by pUKDN115 (Yang et al, 2021). Plasmid expressing IBDV-VP2 was replaced by the void pUKDN115 in KML and KMH to obtain KML void and KMH void , respectively.…”

“…To compare redox states of cells displaying different expression levels of a heterologous protein, two K. marxianus strains, KML and KMH were selected. In our previous study, KM-HPV2 was constructed to express infectious Frontiers in Bioengineering and Biotechnology frontiersin.org bursal disease virus (IBDV) capsid VP2 by an episomal vector (Yang et al, 2021). KM-HPV2 was subjected to the H 2 O 2 mutagenesis.…”

Transfer of disulfide bond formation modules via yeast artificial chromosomes promotes the expression of heterologous proteins in Kluyveromyces marxianus

“…Substantial expression was observed for β‐1,4‐endomannanas (6.4 g/l) 5 , endo‐β‐xylanase (6.4 g/l) 5 , and feruloyl esterase (12.2 g/l) 6 in K. marxianus . In the realm of virus‐like particles (VLPs), K. marxianus demonstrated superiority, particularly with VLPs of porcine circovirus type 2 (PCV2, 1.9 g/l) 7 , porcine parvovirus (PPV, 2.5 g/l) 8 , and infectious bursal disease virus (IBDV, 1.89 g/l) 9 , surpassing other microbial and insect systems. Owing to its thermotolerance and wide substrate spectrum, K. marxianus is actively being explored for bioethanol and xylitol production.…”