Class switched bovine ultralong CDR H3 amplicons versus canonical in immune and non-immune tissues

Immunogenetics · 2026-02-23

Within the bovine immune response, a distinct type of immunoglobulin (Ig), known as ultralong complementarity-determining region 3 (CDR3) antibodies, coexists alongside canonical Igs. These ultralong heavy chains (HC) feature a remarkable structure with a lengthened CDR3 of the heavy chain (CDR H3), allowing them to adopt either a smaller and more extended paratope than canonical antibodies. However, very little is known about the distribution of ultralong CDR H3s in cattle tissues and which isotypes they are ultimately associated with. This study analyzed and quantified the amplicons of the five immunoglobulin isotypes (IgM, IgD, IgG, IgA, and IgE) for both the canonical and ultralong CDR H3 throughout 24 Bos taurus tissues. IgH amplicons analysis identified an extensive repertoire of expressed canonical and ultralong CDR H3s of each isotype in most tissues. Ultralong cattle Igs were preferentially switched to the IgG isotype, especially in the medial retropharyngeal lymph node draining the immunization site. Additionally, B cells producing canonical Igs in bone marrow switched most to the IgG isotype. These data suggest that ultralong CDR H3 may be uniquely qualified to handle some antigens. A more comprehensive understanding of isotype and tissue-specific immune responses of these unusual antibodies can provide a deeper insight into their function within the overall cattle immune system, offering unique opportunities for innovations for in both bovine health and human immunotherapeutics.

Maternal Immunization with VP8* mRNA Vaccine Yields Superior Passive Transfer of Rotavirus-Neutralizing Antibodies to Foals

Vaccines · 2026-01-09 · 1 citations

Background: Despite the availability of a killed whole-virus (KV) vaccine, diarrhea caused by equine rotavirus group A (ERVA) remains a significant health concern for foals in the United States. The vaccine is administered to pregnant mares, with foals protected by passive transfer of colostral antibodies. However, KV-induced immunity is only partially protective and maternal antibody levels in foals are often low and wane rapidly. To address these limitations, we developed a mRNA-based ERVA vaccine encoding the highly conserved VP8* protein to evaluate whether it can provide improved immune protection. Methods: Pregnant mares (n = 12 per group) were immunized either at months 8 and 10 of gestation with the VP8* mRNA or at months 8, 9, and 10 of gestation with the KV. Serum samples were collected from mares before and after immunization and from their foals at ages 1, 35, and 49 days. Serum samples were tested by indirect ELISA for VP8*-specific relative antibody concentrations and relative concentrations were compared for effects of study group and sample-time using linear mixed-effects regression. To detect functional antibodies against ERVA, a virus neutralization titer assay was performed to compare titers between mares vaccinated with the mRNA vaccine (and their foals) and unvaccinated control mares (and their foals). Results: Mares vaccinated with VP8* mRNA had significantly (p < 0.05) higher antibody concentrations after foaling than mares in the KV group, and foals of VP8* mRNA-vaccinated mares had significantly (p < 0.05) higher concentrations through age 49 days than foals in the KV group. In addition, the VP8* mRNA vaccine elicited higher titers of ERVA-neutralizing antibodies against both G3 and G14 strains. Conclusions: Longer-lasting, higher concentrations of virus-neutralizing antibodies might provide superior duration of immunity to ERVA in foals from mares vaccinated with VP8* mRNA.

Dietary L-glutamate modulates intestinal mucosal immunity of juvenile hybrid striped bass (Morone saxatilis ♀ × Morone chrysops ♂)

Frontiers in Immunology · 2025-04-10 · 4 citations

Introduction L-Glutamate is a conditionally essential amino acid, meaning it can become essential under specific conditions, like stress or disease. It is an abundant intracellular amino acid crucial in immune responses. Supplementation of feed with key amino acids, such as glutamate, can optimize growth and have other health benefits for production animals. Most research on dietary amino acid supplementation has focused on mammalian models, thus this research turned to hybrid striped bass, a teleost fish of growing importance to the aquaculture industry. The study investigated the effects of dietary supplementation with 0% or 5% glutamate in hybrid striped bass on intestinal mucosal immunity. Methods The basal purified diet contained crystalline amino acids, including 3% L-glutamate. After an 8-week period of dietary supplementation with 5% glutamate followed by lipopolysaccharide stimulation, the intestinal mucosa was analyzed at the cellular and molecular levels to compare with the head kidney to assess potential changes in immune reactivity. Results One week after lipopolysaccharide stimulation, glutamate supplementation enhanced ( P < 0.05) the whole-body growth of fish without lipopolysaccharide challenge, total respiratory burst (the sum of O 2 – and H 2 O 2 production) in head kidney leukocytes, the net production of H 2 O 2 in intestinal mucosal leukocytes, and upregulation of expression of mRNAs for IL-1β, TNF-α, and IgT in the gut mucosa. Discussion Dietary supplementation with 5% L-glutamate may modulate intestinal mucosal immunity and improve growth in HSB to enhance disease resistance. Further research is needed to clarify the mechanism and cost-effective application.

Maternal immunization with VP8* mRNA vaccine yields superior passive transfer of rotavirus-neutralizing antibodies to foals

SSRN Electronic Journal · 2025-01-01

Unheralded high MHC Class II polymorphism in the abundant Atlantic herring resolved by long-read sequencing

bioRxiv (Cold Spring Harbor Laboratory) · 2025-06-08

Major Histocompatibility Complex (MHC) genes are the most polymorphic in vertebrate genomes due to their important function of presenting a diversity of peptides from pathogens to initiate an adaptive immune response. Here, we have characterized MHC class II genes and explored their polymorphism and evolution in one of the most abundant vertebrates in the world, Atlantic herring (Clupea harengus). The vast population size and schooling behavior make Atlantic herring an attractive target for pathogens. Hence, we hypothesized that it would maintain exceptionally high MHC polymorphism. We used PacBio HiFi long-read whole genome sequencing data of 14 individuals from three different geographic regions in the Atlantic Ocean and Baltic Sea. The analysis identified nine MHC class II loci distributed across four chromosomes. We found two distinct lineages of class II genes, a highly polymorphic one denoted DA and a non-polymorphic DB lineage, arranged as alpha-beta gene pairs (DAA-DAB or DBA-DBB). The DA genes showed extremely high nucleotide diversity in exon 2, strong signatures of positive selection (dN/dS >> 1) as well as copy number variation. Structure prediction revealed that all highly polymorphic amino acid residues occurred in the predicted peptide binding cleft. Two of the most polymorphic loci showed distinct allelic groupings (supertypes), with high sequence similarity within supertypes and high sequence divergence between supertypes. Most of the haplotypes had genes from different supertypes, thus maintaining diverse class II repertoire in a single individual. There was also a highly significant nonrandom association of DAA and DAB alleles within supertypes, strongly suggesting coevolution of DAA and DAB alleles forming the peptide binding domain. This study reveals that the herring MHC class II genes are among the most, if not the most, polymorphic so far described in vertebrates. Their exceptional polymorphism surpasses that of human due to a larger gene repertoire, copy number variation, and pronounced sequence divergence among alleles. This unheralded polymorphism is most likely explained by the combined effects of the vast population size, minimizing genetic drift, and strong pathogen-driven balancing selection.

Maternal immunization with VP8* mRNA vaccine yields superior passive transfer of rotavirus-neutralizing antibodies to foals

SSRN Electronic Journal · 2025-01-01

Collaborating for the future of medicine

American Journal of Veterinary Research · 2025-10-08

Origin of immunoglobulins and T cell receptors: A candidate gene for invasion by the RAG transposon

Science Advances · 2025-07-04 · 4 citations

Rearranging antigen receptors (AgRs) arose when a variable (V) domain exon was invaded by the recombination-activating gene (RAG) transposon ~500 million years ago. We show here that the elasmobranch immunoglobulin heavy (IgH) isotypes—IgM, IgW, and IgNAR—are linked near the αδ T cell receptor (TCRαδ) locus. This linkage presages the emergence of the osteichthyan IgH translocon arrangement and clarifies the relationship between IgH and TCRδs. Recently, we reported UrIg , a nonrearranging, elasmobranch major histocompatibility complex (MHC)-linked AgR gene. Here, we describe a nonrearranging UrIg paralogue, UrIg2 , linked to this IgM/IgNAR/IgW/TCRαδ gene cluster in an AgR complex (AgRC). UrIg2 amino-terminal domains make homodimers where the C2-C3 structure resembles IgGFc. A relative of the UrIg2 V domain exon was invaded by the RAG transposon, revealing the genesis of the adaptive immune system. Our data indicate that an ancestral chromosome encoded an AgR precursor, undergoing RAG-mediated rearrangement after genome-wide duplication on one chromosome and retaining nonrearranging relics in the MHC and AgRC.

Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi

Molecular Therapy · 2025-06-14 · 2 citations

Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering

Nature Communications · 2024-04-18 · 50 citations

While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.