Field and laboratory findings following the large-scale use of intermediate type infectious bursal disease vaccines in Denmark

Abstract

Following a period of clinical outbreaks of very virulent infectious bursal disease virus (vvIBDV) in Denmark, the histological bursal lesion score (HBLS) was used on a national scale to screen broiler flocks vaccinated with intermediate IBD vaccines for lesions indicative of IBDV challenge. High lesion scores were detected in a high percentage of healthy and well performing flocks despite the lack of other indications of the presence of vvIBDV. RT-PCR and subsequent sequencing showed the frequent presence of H253Q and H253N IBDV strains that were genetically close to the sequence of the intermediate vaccines with a relative risk ratio of 13.0 (P < 0.0001) in intermediate vaccine A or B vaccinated flocks compared to unvaccinated flocks. The relevance of these H253Q and H253N strains was tested under experimental conditions using a protocol derived from the European Pharmacopoeia for safety of live IBD vaccines. The results confirmed the higher pathogenicity for the bursa of these strains compared to intermediate vaccines as well as the negative effect on antibody response to a Newcastle disease (ND) vaccination performed at the peak of the bursa damage. The efficacy of the ND vaccination was still 100% showing that the H253N and H253Q IBDV strains would be considered as safe vaccine viruses. In conclusion, the use of the HBLS to screen commercial broiler flocks vaccinated with intermediate IBD vaccines for the presence of vvIBDV does not seem to be a reliable method due to the frequent occurrence of H253N and H253Q strains in those flocks. For screening of IBD vaccinated flocks for the presence of vvIBDV or other field strains, the RT-PCR with subsequent sequencing seems to be most suitable.

Genome Evolution of Two Genetically Homogeneous Infectious Bursal Disease Virus Strains During Passages in vitro and ex vivo in the Presence of a Mutagenic Nucleoside Analog

“…Since the rCu-1-p0 sequence used in the present study was based on a cell culture adapted Cu-1 strain (Nick et al, 1976), reversion from histidine to glutamine (wild-type residue) at position 253 was expected after passages. Mutations in VP2 at position 253, such as, in most cases, His253Gln, but also His253Asn or His253Asp were indeed observed in vaccine-related viruses isolated from chickens in the field (Olesen et al, 2018). However, in the present study, passages in chickens promoted the apparition of a leucine instead of a glutamine at position 253 in 100% of the viral population, while histidine 253 remained stable in chicken B cells and DF-1 cells.…”

“…Questions about unique genetic mutations involved in the evolution and expansion of vvIBDV remain open. Attenuated vaccines currently used to protect from IBD elicit a more robust immune response when compared to inactivated vaccines, but they convey the risk of reversion toward higher virulence (Olesen et al, 2018;Dey et al, 2019;Eterradossi and Saif, 2020). Thus, a better knowledge of the evolution of IBDV as well as new strategies in the development of safer and more stable vaccines are required to improve the control of emerging IBDV strains.…”

Efficacy of a novel <i>in ovo</i>-attenuated live vaccine and recombinant vaccine against a very virulent infectious bursal disease virus in chickens

“…Attenuated live IBDV vaccines are categorized as mild, intermediate, intermediate-plus, and hot vaccines based on the various attenuation and break-through levels of MDAs [ 13 ]. Intermediate, intermediate-plus, and hot vaccines can be used to better induce neutralizing antibodies against virulent IBDV strains in the field.…”

Ex vivo rescue of recombinant very virulent IBDV using a RNA polymerase II driven system and primary chicken bursal cells

“…We nonetheless used B cells after DF-1 cells transfection to benefit from the high replicative capacity of IBDV in this cell type and obtain high-titer stocks. Serial passage in chickens of an attenuated vaccine strain has been associated with reversions in VP2 positions 253 and/or 284 17,47 , additionally, vaccine-related viruses harboring those changes and associated to severe bursal damages have been detected in the field 47 . It was thus important to check if replication of rCu-1 in B cells during the rescue protocol would result in the appearance of those changes.…”