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Leptospirosis, a globally significant zoonotic disease caused by pathogenic Leptospira, continues to threaten the health and public safety of both humans and animals. Current clinical treatment of leptospirosis mainly relies on antibiotics but their efficacy in severe cases is controversial. Passive immunization has a protective effect in the treatment of infectious diseases. In addition, chicken egg yolk antibody (IgY) has gained increasing attention as a safe passive immunization agent. This study aimed to investigate whether hens produce specific IgY after immunization with inactivated Leptospira and the protective effect of specific IgY against leptospirosis. First, it was demonstrated that specific IgY could be extracted from the eggs of hens vaccinated with inactivated Leptospira and that specific IgY can specifically recognize and bind homotypic Leptospira with a high titre, as shown by MAT and ELISA. Next, we tested the therapeutic effects of IgY in early and late leptospirosis using a hamster model. The results showed that early specific IgY treatment increased the survival rate of hamsters to 100%, alleviated pathological damage to the liver, kidney, and lung, reduced leptospiral burden, and restored haematological indices as well as functional indicators of the liver and kidney. The therapeutic effect of early specific IgY was comparable to that of doxycycline. Late IgY treatment also enhanced the survival rate of hamsters and improved the symptoms of leptospirosis similar to early IgY treatment. However, the therapeutic effect of late IgY treatment was better when combined with doxycycline. Furthermore, no Leptospira colonization was observed in the kidneys, livers, or lungs of the surviving hamsters treated with specific IgY. Mechanistically, IgY was found to inhibit the growth and adhesion to cells of Leptospira. In conclusion, passive immunotherapy with specific IgY can be considered an effective treatment for leptospirosis, and may replace antibiotics regarding its therapeutic effects., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The immunomodulatory (IM) subtype of triple negative breast cancer (TNBC) exhibits high expression of immune cell signaling genes and is more responsive to immunotherapy. However, the specific mechanism underlying this phenomenon remains unclear. One of the potential key genes appears to be the cytotoxic and regulatory T cell molecule (CRTAM). A cohort of 360 previously untreated TNBC patients from Fudan University Shanghai Cancer Center (FUSCC) underwent RNA sequencing analysis of their primary tumor tissue. Combined with three RNA-seq datasets obtained from the GEO database, a LASSO regression analysis was conducted to identify genes specific to the IM type of TNBC. Our findings revealed elevated CRTAM expression in the IM-type TNBC, which correlated with a favorable overall survival and recurrence-free survival in TNBC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated a strong association between CRTAM and immune responses as well as immune system processes. Notably, CRTAM overexpression induced STAT1 phosphorylation and upregulation of interferon-stimulated genes. We also found that CRTAM enhanced tumor-associated immune cell infiltration, especially CD8 + T cells, which may be related to the increased expression of MHC class I molecules caused by CRTAM overexpression. These results suggest that CRTAM may serve as a potential biomarker for predicting the efficacy of immunotherapy in TNBC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is an inhibitory immunoreceptor expressed on lymphocytes that serves as a promising target for cancer immunotherapy. In this study, facile synthetic protocols to produce the extracellular domain of TIGIT were investigated for applications of TIGIT in mirror-image screening. During the synthesis via sequential native chemical ligations, we encountered problems with significantly poor solubility of the ligated products. Introducing trityl-type solubilizing auxiliaries, which also functioned as temporary protecting groups for cysteine residues, facilitated a flexible order of ligations and efficient purification protocols. After refolding under appropriate conditions, the synthetic TIGIT showed a sufficient affinity toward its target ligand CD155., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: A hepatitis B vaccination (HepB) series with an initial dose of hepatitis B immune globulin (HBIG) is the recommended prophylaxis for infants born to mothers with chronic hepatitis B virus (HBV) infection and for HBV-exposed persons without known protection. The HepB and HBIG are administered at different sites (limbs). Instances of HepB and HBIG administered at the same site are documented but the impact on immune responses to HepB remains unanswered., Methods: Newborn and adult BALB/c mice received one dose of HepB at time zero alone or with HBIG in the same or different sites, followed by 2 additional doses of HepB at 3 and 10 weeks (newborn mice) or 4 and 16 weeks (adult mice). To study memory responses mice were given a 4th, booster, dose of HepB at 26 weeks and B cells analyzed., Results: Administration of HepB with HBIG resulted in reduced responses to HepB following the first 2 doses, regardless of site, compared to mice that received HepB only. Lower levels of antibody to HBV surface antigen (anti-HBs) were observed at the end of the 3-dose series (p < 0.0001) in all groups of newborn mice that received HepB and HBIG. In adult mice, this difference was only seen when HepB and HBIG were delivered at the same site. However, following a HepB booster at 26 weeks, HBsAg-specific B-cell expansion and memory phenotype were not impacted by initial HBIG administration CONCLUSION: Administration of HBIG with HepB can delay and reduce responses to HepB in mice. Our findings suggest that the initial circulating levels of HBIG could prevent infection despite an impaired response to vaccine and support the current recommendation of assessing seroprotection after series completion for infants born to HBV carrier mothers, including in cases where vaccine and HBIG are administered incorrectly at the same site., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

IgY-technology (the production and extraction of specific IgY antibodies from egg yolk) is an innovative method to produce antibodies for therapy and prophylaxis. Advantages of IgY over other antibodies comprise its cost-effective extraction, the minimization of animal harm and distress, and its reduced reactivity with mammalian factors. Many research groups have demonstrated that IgY is active against several pathogens or conditions, a fact that may support the design of novel, safe and effective health products. This review provides a comprehensive analysis of IgY-based biologicals for human medicine, including patent applications and clinical trials during the period 2010-2018, and addresses how IgY-technology can lead to innovation in the production of biologicals for the treatment and prophylaxis of a wide range of infectious and non-communicable diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rabies is a fatal zoonotic disease preventable through timely and adequate post-exposure prophylaxis (PEP) to potentially exposed persons i.e. wound washing and antisepsis, a series of intradermal (ID) or intramuscular (IM) rabies vaccinations, and rabies immunoglobulin in WHO category III exposures. The 2010 WHO position on rabies vaccines recommended PEP schedules requiring up to 5 clinic visits over the course of approximately one month. Abridged schedules with less doses have potential to save costs, increase patient compliance, and thereby improve equitable access to life-saving PEP for at-risk populations. We systematically reviewed new evidence since that considered for the 2010 position paper to evaluate (i) the immunogenicity and effectiveness of PEP schedules of reduced dose and duration; (ii) new evidence on effective PEP protocols for special populations; and (iii) the effect of changing routes of administration (ID or IM) during a single course of PEP. Our search identified a total of 14 relevant studies. The identified studies supported a reduction in dose or duration of rabies PEP schedules. The 1-week, 2-site ID PEP schedule was found to be most advantageous, as it was safe, immunogenic, supported by clinical outcome data and involved the least direct costs (i.e. cost of vaccine) compared to other schedules. To supplement this evidence, as yet unpublished additional data were reviewed to support the strength of the recommendations. Evidence suggests that changes in the rabies vaccine product and/or the route of administration during PEP is possible. Few studies have evaluated PEP schedules in persons with suspect or confirmed rabies exposures. Gaps exist in understanding the safety and immunogenicity of novel PEP schedules in special populations such as infants and immunocompromised individuals. Available data indicate that administering rabies vaccines during pregnancy is safe and effective., (Copyright © 2019. Published by Elsevier Ltd.)

The development of human rabies vaccines has evolved dramatically from the first crude nerve tissue vaccine produced then administered in the presence of Louis Pasteur in 1885. New cell culture technology has enabled highly potent and well-tolerated rabies vaccines to be produced that have reduced the volume and number of doses required to save human lives after exposure. However, these highly potent vaccines are still unaffordable to many patients living at risk of exposure on a daily basis. The cost of post-exposure prophylaxis (PEP) is not only related to the direct cost of rabies biologicals and equipment but is also associated with indirect costs that patients incur as a result of travel, loss of work time (income loss), and accommodation over the period of time that a PEP regimen requires to be completed. This paper summarizes the particular criteria that the SAGE Working Group and WHO personnel reviewed as part of the evaluation process for recommending the new one-week intradermal vaccination regimen (2-2-2-0-0) for rabies post-exposure prophylaxis. These criteria included: Cost-effectiveness; evaluation of number of doses; seroconversion after vaccination; efficacy; safety; and patient follow-up., (Copyright © 2018. Published by Elsevier Ltd.)

Our understanding of how equine immunoglobulin genes are organized has increased significantly in recent years. For equine heavy chains, 52 IGHV, 40 IGHD, 8 IGHJ and 11 IGHC are present. Seven of these IGHCs are gamma chain genes. Sequence diversity is increasing between fetal, neonatal, foal and adult age. The kappa light chain contains 60 IGKV, 5 IGKJ and 1 IGKC, whereas there are 144 IGLV, 7 IGLJ, and 7 IGLC for the lambda light chain, which is expressed predominantly in horses. Significant transcriptional differences for IGLV and IGLC are identified in different breeds. Allotypic and allelic variants are observed for IGLC1, IGLC5, and IGLC6/7, and two IGLV pseudogenes are also transcribed. During age development, a decrease in IGLVs is noted, although nucleotide diversity and significant differences in gene usage increased. The following paper suggests a standardization of the existing nomenclature of immunoglobulin genes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Immunity in insects has largely focused on responses towards bacteria and fungi, but recently the study of immune responses against viral infections has also received attention. In Lepidoptera, phagocytosis and encapsulation mediated by hemocytes, and apoptosis are part of the response against virus infection; however, many studies also suggest the presence of unknown factors involved in the anti-viral defense. An up-regulation of the lepidopteran-specific pattern recognition protein Hemolin after baculovirus infection in the Chinese oak silkmoth and discovery of putative virus responsive elements in the up-stream regions of Hemolin in the Cecropia moth and the Tobacco horn worm could suggest that Hemolin is involved in virus defense. In this paper, a number of studies investigating baculovirus pathogenesis, and others analyzing Hemolin expression have been revisited leading to the speculation that Hemolin could be engaged in several anti-viral processes.

All fibrinogen (FBG)-bearing proteins documented to date in the freshwater snail Biomphalaria glabrata, the intermediate host of the human blood fluke Schistosoma mansoni, possess the same molecular structure; one or two immunoglobin superfamily (IgSF) domains at the N-terminus and a FBG domain at the C-terminus (named as FBG-related protein (FREP)). Here we report two novel genes that encode FBG-bearing proteins from B. glabrata. Different from all known FREPs, the first gene encodes a protein (657 amino acids (aa)) composed of a long N-terminal region with no sequence homology to any known protein, a middle epidermal growth factor (EGF) repeat region and a C-terminal FBG domain, designated FBG-related molecule (FReM). Differential expression at 2 days post-exposure (dpe) to the trematode S. mansoni or Echinostoma paraensei was found in the S. mansoni susceptible M line and resistant BS-90 snail strains. The second gene is a new member of the FREP family, designated FREP14, which encodes a 399 aa putative secreted protein. FREP14 is different from known FREPs in that it is encoded by a single locus and is not upregulated in early or late stage S. mansoni exposure, but is upregulated in late stage E. paraensei infection. Furthermore, gene expression during the snail's ontogenesis and at a late stage of trematode infection (52 dpe) has been investigated in the two newly identified genes (FReM and FREP14) described in this paper and five representative members of known FREPs (FREPs 2, 3, 4, 12, and 13). A variety of expression patterns were observed, suggestive of functional diversity among the members of FBG-bearing proteins. Our findings further broaden our understanding of the diversity and function of the FBG-bearing protein encoded genes in B. glabrata.

IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and for the V-LIKE-DOMAINs. In this paper, this standardized characterization is extended to the constant domains (C-DOMAINs), and to the C-LIKE-DOMAINs, leading, for the first time, to their standardized description of mutations, allelic polymorphisms, two-dimensional (2D) representations and tridimensional (3D) structures. The IMGT unique numbering is, therefore, highly valuable for the comparative, structural or evolutionary studies of the immunoglobulin superfamily (IgSF) domains, V-DOMAINs and C-DOMAINs of IG and TR in vertebrates, and V-LIKE-DOMAINs and C-LIKE-DOMAINs of proteins other than IG and TR, in any species.

The identification of new vaccine candidates for leptospirosis is of great interest. This paper describes the identification of two homologous immunogenic proteins, LigA-m and LigB-m, of Leptospira interrogans serovar manilae strain UP-MMC-NIID, which show strong similarity with LigA found recently in L. interrogans serovar pomona. Southern blot analysis indicated the conservation of the lig genes among pathogenic leptospires. LigA-m protein was shown to be a surface-exposed lipoprotein expressed during in vitro culture. Both LigA-m and LigB-m induced protective immunity against a challenge with a homologous serovar of L. interrogans in mice. Furthermore, patients' sera infected with heterologous serovars' strains contained antibodies against LigA-m and LigB-m. Our results suggest that LigA-m and LigB-m proteins are new vaccine candidates for the prevention of leptospirosis.

Until recently, studies of marsupial immunoglobulins were limited to primarily protein analyses, such as Protein A binding and immunological cross-reactivity to eutherian immunoglobulins to draw conclusions about the isotypes present in metatherians. This left an interesting gap in our knowledge of the evolution of vertebrate, more specifically mammalian, antibodies and provided little insight into the diversity of marsupial antibodies. Recently, however, there has been a flurry of papers from multiple laboratories describing, at the molecular level, the heavy and light chain classes present in marsupials with some analysis of the expressed repertoires. These studies have provided the evidence to determine when some of the uniquely mammalian isotypes, e.g. IgG and IgE, appeared in evolution, and are a first look at the complexity of heavy and light chain variable regions in a metatherian. Here we review what was known prior to the cloning of marsupial Ig genes and what we have learned recently.