Biology subjects

Woodyear, S.

Publications and source records attributed to Woodyear, S..

3 recordsLinked to original sources

bioRxiv2025

Quantifying maternal antibody transfer to colostrum and cord blood reveals virus-specific selectivity in dogs

BackgroundNeonatal infections are a leading cause of mortality in dogs, with up to 30% of puppies dying within the first three weeks of life. During this period of immune development, protection is highly dependent on maternal antibodies (MatAbs) transferred across the placenta and via colostrum. Despite the critical importance of this transfer, little is known about the biological or clinical factors that determine its magnitude, whether specific antibodies are preferentially transferred, or how these processes vary across a broad population of dogs. MethodsTo quantify and explore the determinants of MatAb transfer in dogs, we analyzed matched maternal serum, cord blood, and colostrum samples collected from 44 client-owned dams undergoing cesarean section at a university veterinary hospital. Total IgG and virus-specific antibodies against canine parvovirus (CPV) and canine distemper virus (CDV) were analyzed. We also evaluated the influence of maternal factors, including age, breed, body weight, parity and litter size on MatAb transfer efficiency. ResultsAcross this diverse population, we observed limited transplacental transfer of MatAbs (4.5-6% maternal titer), in agreement with previous studies and as expected with the endotheliochorial placenta of dogs. In contrast, virus-specific IgG was highly enriched in colostrum, with 10.7-fold (CPV) and 8.1-fold (CDV) increases relative to serum. Transfer efficiency was significantly greater for virus-specific antibodies than for total IgG (3.2-fold), suggesting selective enrichment of antiviral antibodies during colostrogenesis. Maternal serum antibody titer emerged as the primary factor influencing the efficiency of antibody transfer. ConclusionsThese findings provide the most comprehensive quantification to date of MatAb transfer routes in dogs, revealing preferential transfer of virus-specific IgG to colostrum and highlighting the crucial role of colostrum intake for neonatal immunity. This work establishes a foundation for identifying antibody characteristics that influence MatAb transfer efficiency and reiterates the importance of ensuring dams have adequate titers of virus-specific IgG prior to breeding.

immunology↗

bioRxiv2025

Humanizing a CD28 signaling domain affects CD8 activation, exhaustion and stem-like precursors

CD28 ligation provides critical signals that modulate activated T cell fate. In a human to mouse reverse-engineering approach, a single amino acid substitution adjacent to the C-terminal proline-rich domain created CD28A210P mice with enhanced signaling. CD28A210P mice experienced pro-inflammatory responses to CD28 superagonist antibody, analogous to severe cytokine storm induced in a human clinical trial, with a striking increase of activated CD8 T cells. In acute and chronic viral infections, early activation and expansion of CD28A210P CD8 effector T cells increased, with accelerated exhaustion in chronic infection. Mechanistically, CD28A210P enhanced JunB, IL-2, and inhibitory receptors driven by MEK1/2. Generation of CD28A210P stem-like progenitor (Tpex) cells was enhanced in acute and chronic infections, and further expanded by PD-L1 blockade in chronically-infected mice. Thus, humanized PYAP mice reveal key roles for CD28 signaling strength in CD8 activation, accelerating exhaustion during antigen persistence, while promoting and sustaining Tpex during acute and chronic viral infection. One sentence SummaryA single amino acid substitution adjacent to PYAP to humanize CD28 signaling enhances superagonist response, early CD8 activation and Tpex generation during viral infection while accelerating exhaustion and sustaining Tpex during chronic infection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/642460v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@13fc9f9org.highwire.dtl.DTLVardef@e50762org.highwire.dtl.DTLVardef@47c8eeorg.highwire.dtl.DTLVardef@d892d7_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO Humanized CD28 PYAPP enhances numbers of CD8 T cell effectors and stem-like precursors during acute viral infection, and accelerates exhaustion while sustaining increased self-renewing Tpex cells that are favored during PD-L1 blockade. C_FIG

immunology↗

bioRxiv2025

Mechanisms of maternal antibody interference to rotavirus vaccination

Maternal antibodies (MatAbs) are transferred transplacentally during pregnancy and through breast milk after birth to provide protection whilst the neonatal immune response is immature. However, MatAbs also suppress the development of neonatal B cell responses via mechanisms that are not well defined. MatAbs can therefore result in poor vaccine performance in the infant, placing them at risk against potentially life-threatening pathogens such as rotavirus. It is essential we understand the mechanisms by which MatAbs interact with neonatal immunity, so that strategies can be developed to overcome this major vaccine issue. To investigate mechanisms of interference we developed a mouse model of neonatal oral rotavirus vaccination in the presence and absence of MatAbs. Oral vaccination with attenuated murine rotavirus induced robust neonatal antibody responses, whereas vaccination failed to induce seroconversion in the presence of MatAbs. Vaccination with heterologous strains, reduced MatAb titers and vaccination in Fc{gamma}RIIB knockout mice did not overcome interference. However, live vaccine replication was blocked in the presence of MatAbs and more rapid waning of MatAbs was observed following vaccination. This is indicative of premature vaccine clearance and likely reduced antigen encounter by B cells. Single-cell RNA sequencing of mesenteric lymph nodes revealed diminished plasma and germinal center B cell subpopulations as well as global reduction of interferon-stimulated genes in the presence of MatAbs. Our model has also enabled identification of strategies to reduce the effects of interference. In summary, we have tested multiple hypotheses for MatAb-mediated interference to rotavirus vaccination in a mouse model, and demonstrated that premature Fc{gamma}RIIB signaling and epitope masking are not the primary mechanisms of vaccine failure. Rather our data supports the conclusion that MatAb-mediated vaccine clearance is a key mechanism of interference to oral rotavirus vaccine.

immunology↗