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[This corrects the article DOI: 10.3389/fimmu.2020.562282.].

Swine acute diarrhoea syndrome coronavirus (SADS-CoV) causes vomiting, severe diarrhoea and death in newborn piglets. The spike (S) protein plays a crucial role in promoting virus invasion and inducing neutralizing antibody production. In this study, the extracellular region of the S protein was used as an immunogen to immunize BALB/c mice. After immunization, B cells were collected, fused with SP2/0 myeloma cells, cultured and subcloned, and a cell line capable of secreting neutralizing antibodies was obtained and named as 5D6. Additionally, it was determined that the 5D6 mAb could be used as the primary antibody for western blotting and indirect immunofluorescence assay (IFA) to detect SADS-CoV. Further studies indicated that the 5D6 mAb binds to the 136 STSHAAD 142 motif, which located in the N-terminal domain (NTD) of the spike protein. This result suggested that the NTD of the S protein can induce the production of neutralizing antibodies. Amino acid sequence alignment revealed that the epitope of the 5D6 mAb was conserved among SADS-CoV strains. This study helps elucidate the S protein function of SADS-CoV, and the 5D6 mAb may be used to develop diagnostic and treatment tools for detecting SADS-CoV infection.

Accurate information on antigenic epitopes within a multi-domain antigen would provide insights into vaccine design and immunotherapy. The multi-domain outer surface Leptospira immunoglobulin-like (Lig) proteins LigA and LigB, consisting of 12–13 homologous bacterial Ig (Big)-like domains, are potential antigens of Leptospira interrogans . Currently, no effective vaccine is available against pathogenic Leptospira . Both the humoral immunity and cell-mediated immunity of the host play critical roles in defending against Leptospira infection. Here, we used immunoinformatics approaches to evaluate antigenic B-cell lymphocyte (BCL) and cytotoxic T-lymphocyte (CTL) epitopes from Lig proteins. Based on certain crucial parameters, potential epitopes that can stimulate both types of adaptive immune responses were selected to design a chimeric vaccine construct. Additionally, an adjuvant, the mycobacterial heparin-binding hemagglutinin adhesin (HBHA), was incorporated into the final multi-epitope vaccine construct with a suitable linker. The final construct was further scored for its antigenicity, allergenicity, and physicochemical parameters. A three-dimensional (3D) modeled construct of the vaccine was implied to interact with Toll-like receptor 4 (TLR4) using molecular docking. The stability of the vaccine construct with TLR4 was predicted with molecular dynamics simulation. Our results demonstrate the application of immunoinformatics and structure biology strategies to develop an epitope-specific chimeric vaccine from multi-domain proteins. The current findings will be useful for future experimental validation to ratify the immunogenicity of the chimera.

Porcine deltacoronavirus (PDCoV) is an emerging enteric pathogen that causes substantial economic losses in the swine industry worldwide. The PDCoV NS6 protein is an accessory protein that plays a pivotal role in the viral life cycle and immune evasion. However, the functions of NS6 and its role in PDCoV pathogenesis remain largely unknown. In this study, we prepared a monoclonal antibody (mAb) 5-A11 that specifically recognizes the PDCoV NS6 protein. The mAb 5-A11 exhibited high specificity for PDCoV, with no cross-reactivity with several major porcine pathogenic viruses. Furthermore, the epitope recognized by mAb 5-A11 was precisely mapped to residues 70EYGSIYGKDFI80 of the NS6 protein using Western blot analysis. Notably, this epitope is highly conserved among different PDCoV isolates. Substantial variations were observed when comparing this epitope with the corresponding regions in the NS6 proteins of other δ coronaviruses, suggesting potential differences in the structure, function, and antigenicity of their NS6 proteins. Our findings provide valuable tools and insights for further elucidating the functions of the NS6 protein and its role in PDCoV pathogenesis, as well as for developing diagnostic and therapeutic strategies against PDCoV infection.

Porcine deltacoronavirus (PDCoV) is an emerging virus that poses a significant threat to the global swine industry. Its membrane (M) protein is crucial for virion assembly and virus–host interactions. We selected the hydrophilic region of M protein for prokaryotic expression, purification, and recombinant protein production. Utilizing hybridoma technology, we prepared the monoclonal antibody (mAb) 24-A6 against M protein. The mAb 24-A6 was shown to be suitable for use in immunofluorescence assays, western blotting, and immunoprecipitation, with specificity for PDCoV and no cross-reactivity with other five porcine viruses. The M protein was observed to be expressed as early as 3 h after PDCoV infection, increasing its expression over the duration of infection. Notably, the antigenic epitope of the M protein identified as 103SPESRL108 recognized by mAb 24-A6 was found within a conserved structural domain (SWWSFNPETNNL) of the coronavirus M protein, indicating a crucial overlap between a functionally important viral assembly region and a region recognized by the immune system. Our findings provide valuable insights into mAb 24-A6 targeting the antigenic epitope of M protein and may contribute to the development of diagnostic tools for PDCoV infection and fundamental research into the function of PDCoV M protein.

Group A rotavirus (RVA) is the leading cause of acute gastroenteritis in infants and young children worldwide. To elucidate the molecular epidemiology of G2P[4] rotavirus in China and the protective effects of vaccines, whole-genome analysis of 13 G2P[4] RVA strains collected from China in 2022 was performed. Twelve strains possessed the typical DS-1-like genome constellation G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2. Only GS2265 possessed the genome constellation G2-P[4]-12-R2-C2-M2-A2-N2-T2-E1-H2. With the exception of the NSP4 segment of GS2265, all other sequences of the 13 G2P[4] RVA strains clustered within the same lineage on phylogenetic analysis. However, QD2210 and SX2205 were grouped into different branches compared to the other strains. In the VP7 antigenic epitopes, four residues differed from the RotaTeq G2 strain; specifically, A87T and D96N in the 7-1a region and S213D and S242N in the 7-1b region. Comparison of the current G2P[4] RVA strains circulating in China with those circulating globally revealed a high degree of sequence identity. High genetic variability among the newly characterized G2P[4] RVA strains suggest the strains evolve fast. Finally, our data suggest that the multivalent RotaTeq vaccine could have provided better protection than the monovalent Rotarix and LLR.

Transient receptor potential melastatin 4 (TRPM4) channel, a monovalent cation channel, plays a crucial role in various neurological disorders. We previously showed that TRPM4 activity can be blocked by our antibodies: M4P, which targets rat TRPM4 and M4M, against a similar antigenic epitope of human TRPM4. M4P and M4M demonstrated efficacy in mitigating stroke reperfusion injury. To facilitate human application, M4M was humanized through CDR grafting, resulting in human IgG1 antibodies (Ab1-6). These antibodies were evaluated for their binding affinity, surface staining, stability, and functional inhibition of the human TRPM4 channel. Ab6 (renamed as M4H) was selected and inhibited TRPM4 currents in human brain microvascular endothelial cells under ATP depletion conditions. Importantly, Ab6 (M4H) suppressed ATP depletion-induced cell swelling, indicating its potential for managing vascular injury in ischemic brain diseases. Future studies on animal models could advance the development of novel therapies of neurological disorders with vascular injury.

[This corrects the article DOI: 10.3389/fcimb.2022.927490.].

Membranous nephropathy (MN), an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. In 80% of cases, the specific etiology of MN remains unknown, while the remaining cases are linked to drug use or underlying conditions like systemic lupus erythematosus, hepatitis B virus, or malignancy. Although about one‐third of patients may achieve spontaneous complete or partial remission with conservative management, another third face an elevated risk of disease progression, potentially leading to end‐stage renal disease within 10 years. The identification of phospholipase A2 receptor as the primary target antigen in MN has brought about a significant shift in disease management and monitoring. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression. By synthesizing the latest research findings and clinical insights, this review seeks to contribute to the ongoing efforts to enhance our understanding and management of this challenging autoimmune disorder. Membranous nephropathy, an autoimmune disease, can manifest at any age and is among the most common causes of nephrotic syndrome in adults. This review explores recent advancements in the pathophysiology of MN, encompassing pathogenesis, clinical presentations, diagnostic criteria, treatment options, and prognosis, with a focus on emerging developments in pathogenesis and therapeutic strategies aimed at halting disease progression .

Background Transmissible gastroenteritis virus (TGEV) is a devastating coronavirus that causes severe gastrointestinal symptoms and high mortality in piglets, resulting in substantial economic losses in the swine industry. The spike (S) protein, particularly its S2 subunit, plays a crucial role in virus-host membrane fusion and exhibits high conservation among TGEV strains. However, B-cell epitopes within the TGEV S2 protein remain largely uncharacterized. This study aimed to express and purify the TGEV S2 protein, generate monoclonal antibodies (mAbs) against it, and identify specific B-cell epitopes. Results We successfully expressed and purified the TGEV S2 protein using a prokaryotic expression system. Immunization of BALB/c mice with the purified S2 protein yielded mAb 12G8, characterized as an IgG2b isotype with a kappa light chain. The mAb 12G8 demonstrated specific reactivity against TGEV strains through multiple immunological assays. Epitope mapping identified 1109 QGQALS 1114 as the minimal B-cell specific epitope recognized by mAb 12G8, which exhibits high conservation across different TGEV strains. Three-dimensional structural modeling analysis localized this conserved epitope within the heptad repeat 1 domain of TGEV S2 protein. Conclusions These findings advance the understanding of TGEV S2 protein antigenicity and provide valuable resources for developing improved diagnostic tools and therapeutic strategies against TGEV infection. The identification of a conserved B-cell epitope within the S2 protein establishes new avenues for targeted vaccine development and may contribute to more effective control measures against TGEV in the swine industry.