Infectious Bursal Disease (IBD) is an immunosuppressive viral disease caused by the Infectious Bursal Disease Virus (IBDV). It primarily affects young chickens, targeting the bursa of Fabricius, and poses significant economic threats to the poultry industry. To date, in addition to strict biosecurity measures, large-scale immunization is the optimal strategy and effective method to prevent and control IBDV infection. The emergence of new variant strains has made it more urgent to develop new vaccination strategies against IBD. Over the past few decades, many high-quality vaccines have been available on the market for the control of IBD, which can provide solid protection against the infections and diseases caused by classic IBDV to very virulent IBDV that had been continuously evolving and were endemic worldwide. However, viruses are not static. As they continue to circulate and evolve in the fields, novel antigenic variant viruses have been emerged in the last few years, and vaccines need to keep up with their pace. Collectively, this review summarizes the strategic evolution of IBDV vaccines from traditional methods to cutting-edge molecular platforms, providing promising strategies for developing the next-generation vaccines with higher safety, efficacy, and the ability to keep pace with the antigenic drift in IBDV.
Pasteurella multocida is a zoonotic pathogen responsible for severe diseases in domestic and wild animals, posing threats to public health and causing substantial economic losses. Here, we describe a naturally attenuated P. multocida strain, FCF147, isolated from a mortality event involving black-necked swans (Cygnus melancoryphus) in a wildlife habitat in Fujian, China. Genomic and phylogenetic analyses revealed that FCF147 is evolutionarily distant from other P. multocida lineages and lacks the entire capsule gene cluster. Morphological observations revealed that the loss of the capsule exposed proteins on the bacterial surface. Phenotypic characterization demonstrated reduced capsule production, enhanced biofilm formation, and increased tolerance to heat stress. In vivo infection models confirmed that FCF147 exhibits markedly attenuated virulence in both mice and poultry. However, immunization with FCF147 did not provide effective protection against the challenge of a virulent capsular type A strain. These findings suggest that while FCF147 is poorly virulent, its ability to form robust biofilms and survive thermal stress may facilitate persistence in wild bird reservoirs and potential transmission routes. These findings offer novel insights into the ecological adaptation and pathogenic potential of naturally capsule-deficient P. multocida in wildlife, highlighting their relevance to wildlife surveillance and disease ecology.
Since 2021, an epidemic disease characterized with hydrosalpinx fluid syndrome (HFS) has been circulating in the laying Sheldrake ducks in China, which seriously endangers the healthy development of the duck industry. The causative agent of this disease has been traced to avian metapneumovirus subtype C (aMPV/C), known to cause acute upper respiratory tract infections and egg-drop in poultry. To date, no reports have been made to isolate and characterize aMPV/C infection in Sheldrake ducks in China. Here, a strain of virus, designated aMPV-FJ21, was successfully isolated from the diseased ducks exhibiting HFS. Transmission electron microscopy revealed that the virus is an enveloped particle exhibiting a spherical or pleomorphic morphology. Indirect immunofluorescence assays demonstrated that the aMPV-FJ21 strain had an obvious reactive activity with the ploy-antibody against aMPV/C F protein. The complete genome of aMPV-FJ21 was determined to be 14,149 nucleotides in length. Notably, the amino acid sequence of the G protein was only 55.6%-78.7% identical to those of other aMPV/C reference strains. Phylogenetic analysis indicated that aMPV-FJ21 forms a distinct lineage within the aMPV/C group and is genetically distant from the North American and Eurasian lineages, suggesting that it may represent a novel genetic lineage. In challenge experiments, laying Sheldrake ducks with aMPV-FJ21 reproduced the typical clinical symptoms and pathological lesions observed in the field cases. Altogether, we had isolated a novel aMPV/C variant from Sheldrake ducks exhibiting HFS, distinct from previously reported strains, and provided the first evidence confirming its role as the causative agent of HFS in ducks.
Pasteurella multocida (Pm) is a zoonotic pathogen that poses a significant threat to animal health and causes substantial economic losses, further aggravated by rising tetracycline resistance. To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity of doxycycline combined with metformin, an FDA-approved antidiabetic agent. Among several non-antibiotic adjuvant candidates, metformin exhibited the most potent in vitro synergy with doxycycline, especially against capsular serogroup A strain (PmA). The combination demonstrated minimal cytotoxicity and hemolysis in both mammalian and avian cells and effectively inhibited resistance development under doxycycline pressure. At 50 mg/kg each, the combination of metformin and doxycycline significantly reduced mortality in mice and ducks acutely infected with PmA (from 100% to 60%), decreased pulmonary bacterial burdens, and alleviated tissue inflammation and damage. Mechanistic validation confirmed that metformin enhances membrane permeability in Pm without compromising membrane integrity, dissipates membrane potential, increases intracellular doxycycline accumulation, and downregulates the transcription of the tetracycline efflux gene tet(B). Morphological analyses further revealed pronounced membrane deformation and possible leakage of intracellular contents. These findings highlight metformin as a potent, low-toxicity tetracycline adjuvant with cross-species efficacy, offering a promising therapeutic approach for managing tetracycline-resistant Pm infections.
Three immunoglobulin (Ig) isotypes have been identified in teleosts, IgM, IgD, and IgT or IgZ. IgT, a new teleost Ig isotype, plays a vital role in mucosal immunity. However, information on molecular and functional characteristics of fish IgT is still limited. In this study, an IgT heavy chain (LcIgT) gene was cloned and characterized in large yellow croaker (Larimichthys crocea). Complete cDNA of LcIgT was 1930 bp in length, encoding a protein of 554 amino acids. The deduced LcIgT contains a VH region and only three CH regions (CH1, CH2, CH4), but no transmembrane region was predicted. Phylogenetic analysis showed that IgT heavy chain sequences from all fish species are grouped together. Homology comparison showed that LcIgT shares the highest amino acid identity of 58.73% with IgT heavy chain in Scophthalmus maximus. The VH domain of LcIgT has the highest identity of 72.50% with that of Scophthalmus maximus IgT. Relatively, each constant domain of LcIgT exhibits the highest amino acid identity with that of IgT in Oreochromis niloticus (67.61% identity for CH1, 61.11% identity for CH2, and 63.74% identity for CH4). LcIgT was constitutively expressed in various tissues tested, with the highest levels in mucosa-associated tissues such as gills and skin. After Cryptocaryon irritans infection, the mRNA levels of LcIgT were significantly up-regulated in the spleen (3.27-fold) at 4 d, in the head kidney (3.98-fold) and skin (2.11-fold) at 7 d, and in gills (4.45-fold) at 14 d. The protein levels in these detected tissues were all significantly up-regulated; the peak of its up-regulation was 6.33-fold at 28d in gills, 3.44-fold at 7d in skin, and 3.72-fold at 14d in spleen. These results showed that IgT response could be simultaneously induced in both systemic and mucosal tissues after parasitic infection and that IgT may be involved in systemic immunity and mucosal immunity against parasitic infection.