Biology subjects

Ober, E.

Publications and source records attributed to Ober, E..

7 recordsLinked to original sources

bioRxiv2026

Maternal vaccination timing shapes the composition and maturation of antibody clonotypes transferred to the newborn

Newborns rely on maternally transferred antibodies for immune protection, acquired across the placenta and through breast milk. Despite this importance, how closely the inherited antibody repertoire resembles the mothers has not been examined at the clonotypic level. We combined BCR-Seq with proteomic Ig-Seq to track SARS-CoV-2-specific antibody clonotypes across maternal blood, cord blood, and breast milk from six mRNA-immunized pregnant individuals. Vaccination earlier in gestation generated more diverse peak IgG repertoires but greater contraction before delivery, yielding fewer transferred clonotypes. Vaccination later in gestation produced more restricted peak repertoires, but more clonotypes persisted to delivery and transferred to cord. Infant cord was enriched for persistent, highly somatically mutated, and intraclonally diverse IgG clonotypes, consistent with preferential transfer of affinity-matured antibodies. In contrast, breast milk IgA repertoires were largely distinct from systemic repertoires and underwent substantial remodeling despite stable antigen titers. These findings define molecular determinants of passive immunity shaped by vaccination timing relevant to optimizing maternal immunization.

immunology↗

bioRxiv2026

Transgene Expression Kinetics and Replication Potential of Recombinant Adenovirus Serotype 4 in a Mouse Model and its Use as a Herpes Simplex Virus Vaccine

Human adenovirus serotype 4 (Ad4) is used as a replication-competent oral vaccine that safely and effectively prevents Ad4 respiratory illness in US military personnel. Recombinant Ad4 vaccine candidates elicit mucosal and systemic immune responses against respiratory viruses in hamsters, nonhuman primates, and humans. Although evaluation of Ad4 vaccine candidates in mice would be extremely useful given the large number of immunologic tools available, this has been limited by concerns about a lack of viral replication in these animals. Here we generated recombinant Ad4 vectors that express either luciferase (Ad4-Luc) or herpes simplex virus type 2 (HSV-2) glycoprotein D (Ad4-gD2) to identify transgene expression kinetics, the presence of Ad4 vector replication, and HSV-2 immune responses and protection against HSV-2 infection. Local luciferase activity was observed from 7 hours to 20 days after intranasal inoculation of BALB/c and humanized mice. Subsequent inoculations with Ad4-Luc showed reduced luciferase expression in BALB/c mice, but robust expression in humanized mice, suggesting an immune response to the vector in wild-type mice. Ad4 DNA, but not luciferase activity, was reduced in the lungs of BALB/c mice treated with cidofovir before inoculation with Ad4, implying that Ad4 replicated, albeit at a low level, in the lungs. Intranasal vaccination of mice with Ad4-gD2 resulted in HSV-2 neutralizing antibody in the serum, and after HSV-2 intravaginal challenge reduced disease scores, increased survival, and reduced shedding. Overall, the BALB/c mouse model is semi-permissive to Ad4 mucosal infection, but transgene expression is sufficient for the study of Ad4-based vaccine candidates. ImportanceMucosal surfaces serve as the primary site of infection and shedding for many viral pathogens. Immune responses at mucosal sites provide protection, but few mucosal vaccines are licensed. The oral replication-competent adenovirus serotype 4 (Ad4) vaccine is used to prevent respiratory illness in military recruits, has an extraordinary record of safety and efficacy and has been tested as a recombinant platform for other viruses. Further development of this vaccine platform has been partially hindered by the perceived inability to evaluate vaccine candidates in mice. Here we characterize recombinant Ad4 transgene expression kinetics and viral replication after inoculation at various sites and show protection against herpes simplex virus type 2 (HSV-2) genital disease in mice after intranasal vaccination. We show that Ad4 can induce protective efficacy, even in a semi-permissive mouse model, suggesting this is a promising vector for HSV-2 and potentially other viral pathogens.

immunology↗

bioRxiv2026

Intranasal Replicating Adenovirus type 4-SARS-CoV-2 Recombinants Induce Superior Immune Response Durability and Efficacy in Preclinical Testing Compared to Standard Intramuscular Vaccines

The portfolio of next generation COVID-19 vaccines would benefit from candidates that induce durable systemic and mucosal immune responses that would lessen person-to-person transmission. We constructed an intranasal (IN) replication-competent adenovirus type 4 recombinant platform to express SARS-CoV-2 Spike variants (Ad4-S) and assessed immunogenicity and efficacy in the Syrian hamster model. Although both IN Ad4-S and intramuscular (IM) vaccines (Ad26.CoV2.S and mRNA-1273) induced serum binding antibodies, only Ad4-S induced a robust mucosal response in the nasal cavity. IN Ad4-S vaccination induced serum neutralizing titers equivalent to or greater than IM vaccination but more durable up to 6 months. Upon challenge, IN immunization also resulted in less weight loss, greater breadth and durability of restriction of viral replication, and less lung pathology than IM immunization up to 268 days after immunization. These data support the potential of the IN Ad4 vaccine platform to reduce transmission of SARS-CoV-2 and other respiratory viruses with pandemic potential.

immunology↗

bioRxiv2025

Wheat responds to lack of root hairs with recruitment of bacteria harboring P mineralization genes and increased arbuscular mycorrhizal fungi arbuscularisation

Understanding how crops recruit bacterial and fungal partners for phosphorus (P) nutrition remains incomplete, particularly regarding temporal shifts between P-cycling bacteria and arbuscular mycorrhizal fungi (AMF). We investigated these dynamics using the wheat root hair mutant short root hair 1 (srh1), which is impaired in root hair elongation and may be more dependent on microbial P acquisition compared to the wildtype. We profiled the P-cycling bacterial microbiome and AMF colonization across development and at booting under P-depleted conditions. Before AMF establishment, the root hair mutant rhizosphere was enriched in bacterial organic P-mineralization genes. After AMF colonization increased in both genotypes, this enrichment disappeared, indicating a temporal shift from bacterial to fungal P acquisition. Growing the root hair mutant in P-depleted conditions to booting, when P uptake is highest in wheat, did not induce the mutant to recruit its bacterial P-cycling microbiome. Instead, AMF arbuscule formation was enriched. Collectively, our results reveal a temporal transition in wheat from bacterial to AMF-mediated P nutrition and highlight the compensatory role of the microbiome in plants lacking root hair elongation.

microbiology↗

bioRxiv2023

Arsenite methyltransferase 3 regulates hepatic energy metabolism which dictates the hepatic response to arsenic exposure

Inorganic arsenic (iAs(III)) is among the most pervasive environmental toxicants in the world. The iAs metabolizing enzyme, arsenite methyltransferase (AS3MT), is a key mediator of iAs(III) toxicity and has been almost exclusively investigated in the context of iAs(III) exposure. We use functional genomics approach with zebrafish as3mt mutants which lack arsenite methyltransferase activity to uncover novel, arsenic-independent functions for As3mt. Transcriptomic analysis of untreated whole larvae, and the larval and adult livers from as3mt mutants revealed thousands of differentially expressed genes (DEGs) compared to wild-type controls. These were enriched for genes functioning in the ribosome or mitochondria. Nearly all genes in the citric acid cycle and mitochondrial transport were downregulated in as3mt mutant livers. This resulted in reduction in reactive oxygen species levels by half and fatty liver in 81% of as3mt mutant larvae. An inverse expression pattern was detected for over 2,000 of the As3mt regulated DEGs in the liver of larvae with transgenic overexpression of As3mt in hepatocytes. Replacing as3mt expression in hepatocytes of as3mt mutants prevented fatty liver, demonstrating that As3mt has novel, cell-autonomous and arsenic-independent functions regulating mitochondrial metabolism. We suggest that these functions contribute to iAs toxicity, as the mitochondrial function genes that were downregulated in the liver of unexposed as3mt mutants were further downregulated upon iAs exposure and as3mt mutants were sensitized to iAs. This indicates that As3mt regulates hepatic energy metabolism and demonstrates that, in addition to its role in iAs detoxification, the physiological functions of As3mt contribute to arsenic toxicity. SIGNIFICANCEArsenic is an endemic environmental toxicant, and the current paradigm is that susceptibility to arsenic toxicity is dictated by levels of expression of the arsenite 3 methyltransferase gene (As3mt), which is dedicated enzyme involved in arsenic detoxification. Our data showing that As3mt serves arsenic-independent functions in energy metabolism challenge this paradigm. We show that zebrafish as3mt mutants have loss of mitochondrial function and develop fatty liver and suggest that as3mt mutants are sensitized to arsenic toxicity due, in part, to impaired mitochondrial function. This finding opens an entirely new area of study to identify the cellular function of As3mt and further advances the understanding of how genetic variants in As3mt confer sensitivity arsenic toxicology.

genetics↗

bioRxiv2020

Effects of breeding history and crop management on the root architecture of wheat

AimsSelection for optimal root system architecture (RSA) is important to ensure genetic gains in the sustainable production of wheat (Triticum aestivum L.). Here we examine the idea that past wheat breeding has led to changes in RSA and that future breeding efforts can focus directly on root traits to improve adaptation to a target environment. MethodsWe conducted three field trials using diverse wheat varieties, including modern and historic UK varieties and non-UK landraces, tested under contrasting tillage regimes (non-inversion tillage versus conventional ploughing) or different seeding rates (standard rate versus high rate). We used field excavation, washing and measurement of root crowns ( shovelomics) to characterise RSA traits, including: numbers of seminal, crown and nodal roots per plant, and crown root growth angle. ResultsWe found large differences among genotypes for all root traits. Modern varieties generally had fewer roots per plant than historic varieties. There were fewer crown roots and root angles were wider, on average, under shallow non-inversion tillage compared with conventional ploughing. Crown root numbers per plant also tended to be smaller at a high seeding rate compared with the standard rate. There were significant genotype-by-year, genotype-by-tillage and genotype-by-seeding-rate interactions for many root traits. ConclusionsSmaller root systems is likely to be a result of past selection and may have facilitated historical yield increases by reducing below-ground competition within the crop. The effects of crop management practices on RSA depend on genotype, suggesting that future breeding could select for improved RSA traits in resource-efficient farming systems.

plant biology↗

bioRxiv2018

The effects of training population design on genomic prediction accuracy in wheat

Genomic selection offers several routes for increasing genetic gain or efficiency of plant breeding programs. In various species of livestock there is empirical evidence of increased rates of genetic gain from the use of genomic selection to target different aspects of the breeders equation. Accurate predictions of genomic breeding value are central to this and the design of training sets is in turn central to achieving sufficient levels of accuracy. In summary, small numbers of close relatives and very large numbers of distant relatives are expected to enable accurate predictions.\n\nTo quantify the effect of some of the properties of training sets on the accuracy of genomic selection in crops we performed an extensive field-based winter wheat trial. In summary, this trial involved the construction of 44 F2:4 bi- and triparental populations, from which 2992 lines were grown on four field locations and yield was measured. For each line, genotype data were generated for 25,000 segregating single nucleotide polymorphism markers. The overall heritability of yield was estimated to 0.65, and estimates within individual families ranged between 0.10 and 0.85. Within cross genomic prediction accuracies of yield BLUEs were 0.125 - 0.127 using two different cross-validation approaches, and generally increased with training set size. Using related crosses in training and validation sets generally resulted in higher prediction accuracies than using unrelated crosses. The results of this study emphasize the importance of the training set design in relation to the genetic material to which the resulting prediction model is to be applied.

genetics↗