Biology subjects

Hartmann, S.

Publications and source records attributed to Hartmann, S..

At least 19 recordsLinked to original sources

bioRxiv2026

An ER Retrieval-and-Release System Reveals Ligand-Independent Basal Signaling by Cell Surface TCRs

The T cell receptor (TCR) machinery comprises the ligand-binding TCR{beta} and the CD3 signaling dimers. Individual subunits are synthesized in the endoplasmic reticulum (ER) and only the fully assembled TCRs reach the cell surface. We engineered a system to retained CD3{varepsilon} is in the ER. This allowed only partial TCR assembly, while continuous retrieval of CD3{varepsilon} from the Golgi back to the ER enabled complete assembly. Synchronous TCR release by biotin addition caused a transient increase in surface TCR abundance that gradually returned to steady-state levels. Mathematical modeling revealed that TCR levels were controlled by feedback mechanisms. Notably, surface-localized, but not ER-localized, TCRs spontaneously generated ligand-independent basal signaling. Phosphoproteomic analyses revealed that this signal is similar, but not identical, to ligand-induced TCR activation signals, with distinct phosphorylation patterns already evident at the CD3 subunits. Our findings establish the TCR retrieval-and-release system as a tool to investigate ligand-independent basal TCR signaling.

immunology↗

bioRxiv2026

Liver-Resident Metabolic Reprogramming and Th2/1 Cell Accumulation Drive Anti-Helminth Immunity During H. bakeri InfectionRunning title: Liver metabolic-immune crosstalk in helminth infection

The liver plays a pivotal yet understudied role in anti-helminth immunity. Here, we reveal that during Heligmosomoides bakeri infection, the liver serves as a critical immunological site, accumulating Th2 and Th2/1 hybrid cells through CXCR3-mediated recruitment driven by IFN-gamma and the chemokines CXCL9/10/11. Unlike traditional lymphoid organs, the liver maintains these functional Th2 and Th2/1 cells throughout the chronic and memory phases of infection, exhibiting potent cytokine production and no signs of exhaustion. Transcriptomic analysis of liver tissues uncovered stage-specific metabolic reprogramming, with early H. bakeri infection (6 days p.i.) suppressing oxidative phosphorylation and acute infection (14 days p.i.) activating immune pathways (e.g., TNF, JAK-STAT). Notably, metabolic shifts were independent of T cell infiltration and were instead induced by parasite excretory-secretory products (HES) and alarmins, which disrupted mitochondrial ATP production. The liver's glucose-rich microenvironment supported T cell effector function, including IL-5 production linked to elevated serum IL-5 and bile IgA. Our findings redefine the liver as a dynamic regulator of anti-helminth immunity, integrating metabolic and immune responses to sustain long-term host defense. These insights open new avenues for targeting liver-specific pathways to enhance parasite clearance.

immunology↗

bioRxiv2026

NELLY enables patient-centric drug prioritization through interpretable drug-conditioned gene weighting

Precision oncology seeks to match each tumor with the most effective anti-cancer therapy. Advances in pharmacogenomics and machine learning enabled drug response prediction models with strong performance in cancer cell lines. Nonetheless, patient-centric evaluation of drug prioritization and systematic assessment of model generalization in patient-derived systems across cancer types remain largely absent. Here we introduce a translational framework combining patient-centric benchmarking with a pan-cancer pharmacogenomic atlas of patient-derived organoids, together with NELLY, a deep learning model integrating transcriptomic and chemical information to predict drug response and prioritize therapies. NELLY outperformed existing methods for patient-specific drug prioritization across cancer cell lines and patient-derived organoids, including under out-of-distribution evaluation. Its dynamic weighting mechanism provided patient-specific gene attributions, offering a route to connect predicted drug response to molecular programs associated with drug resistance. Our results support NELLY as a promising framework for translationally relevant and interpretable drug response prediction in precision oncology.

cancer biology↗

bioRxiv2026

Transcriptome of Peripheral Blood Mononuclear Cells Reveals Suppressed MAPK/AP-1 Pathways During Ascaris-Salmonella Coinfection in Pigs

Ascaris and Salmonella are prevalent pathogens in pigs, and their coinfection could pose significant veterinary and public health concern. While Salmonella typically elicits strong monocyte-driven inflammation, we previously showed that A. suum coinfection impairs monocyte responses and increases bacterial burden. Building on these prior observations, we investigated the transcriptional basis of helminth-induced immune modulation using peripheral blood mononuclear cells from experimentally infected pigs. Bulk RNASeq analysis revealed 126 differentially expressed genes in coinfected pigs relative to Salmonella single-infected pigs, including downregulation of genes associated with chemotactic function (CCL3L1, CCL8, CXCL14) linked to monocyte recruitment and macrophage-mediated antimicrobial function. To uncover underlying cellular signaling mechanisms, we applied co-expression network analysis, identifying two modules of interest: one enriched for inflammatory signaling pathways (TNF, IL-17, MAPK), and the other associated with phagosome and lysosome function. Notably, coinfection resulted in selective repression of key genes in the inflammation-related module, including MAPK modulators (DUSP1, DUSP6), AP-1 components (FOS, NR4A1, MAFF), and monocyte activation genes (TNFSF9, CD163), pointing to a potential coordinated shutdown of monocyte inflammatory signaling. These findings reveal that an active Ascaris infection interferes with host immunity against a subsequent bacterial infection by disrupting AP-1/MAPK-dependent transcriptional networks, providing mechanistic insight into helminth-mediated immune modulation.

immunology↗

bioRxiv2025

Controlling TCR and CAR activation by targeting LCK recruitment with a first-in-class small-molecule inhibitor

T-cell activation is driven by the recruitment of lymphocyte-specific protein tyrosine kinase (LCK) to the T-cell receptor (TCR), a critical step in initiating immune responses. Existing LCK inhibitors lack specificity because they target the conserved kinase domain shared by Src family kinases, resulting in off-target effects. Here, we introduce a novel strategy to selectively modulate T-cell activation by disrupting the interaction between the SH3 domain of LCK and the receptor kinase (RK) motif of CD3{varepsilon}. Using computational modeling and high-throughput virtual screening, we identified candidate compounds targeting the SH3(LCK) domain. Functional validation revealed that one compound, C10, selectively disrupted the SH3-RK interaction, leading to reduced TCR-driven activation and proliferation, while sparing activation via alternative receptors and B-cell responses. Moreover, C10 modulated the activity of CD3{varepsilon}-containing CAR and TRuC T cells, attenuating cytokine production and promoting a central-memory-like phenotype associated with enhanced persistence. These findings establish targeted disruption of LCK recruitment as a viable strategy for fine-tuning T-cell responses and propose SH3(LCK) as a druggable domain with therapeutic potential for autoimmune diseases, graft-versus-host disease, and optimizing CAR T-cell therapies.

immunology↗

bioRxiv2025

Time-resolved structures of β2-adrenergic receptor modulation by a photoswitchable beta-blocker

G protein-coupled receptors (GPCRs) regulate essential physiological responses and are important drug targets, yet their ligand-induced conformational dynamics remain poorly understood. The {beta}2-adrenergic receptor ({beta}2AR) is a prominent member of the GPCR family. It regulates bronchial and vascular function and is a significant drug target, particularly in respiratory and smooth muscle-related disorders. We employed time-resolved crystallography at X-ray free-electron lasers (XFELs) to capture the conformational dynamics of {beta}2AR bound to photoazolol-1, a beta-blocker derivative developed for photopharmacological applications. Structural snapshots of the receptor bound to trans-photoazolol-1 (pre-photoconversion), a strained intermediate, and the fully photoisomerized cis-photoazolol-1 reveal an intricate interplay between ligand chemistry and receptor plasticity. Isomerization of the azobenzene moiety induces distinct conformational changes within the orthosteric pocket, altering interactions with the extracellular loop 2 and transmembrane helices 5 and 6. Supported by functional assays, these structural shifts suggest that photoazolol-1 transitions from an inverse agonist to a neutral antagonist upon photoactivation. Our findings uncover a mechanism of GPCR modulation reminiscent of rhodopsin activation and offer a framework for designing ligands that harness light-driven transitions to achieve spatiotemporal control of receptor function.

biochemistry↗

bioRxiv2025

TGFb-induced SMAD1/5 activation drives transient epithelial-to-mesenchymal transition in trophoblasts

Successful human placental development requires fetal trophoblasts to undergo epithelial-to-mesenchymal and mesenchymal-to-endothelial transitions, enabling invasion and remodeling of maternal spiral arteries for proper placental perfusion. These trans-differentiation processes are disrupted in preeclampsia, a major cause of maternal and fetal morbidity worldwide. Despite its clinical significance, the molecular mechanisms governing these differentiation trajectories at the fetal-maternal interface remain poorly defined. While Transforming Growth Factor-beta (TGF{beta}) has been implicated in trophoblast invasion, its role remains controversial. In this study, we report increased SMAD2/3 phosphorylation (pSMAD2/3), but reduced pSMAD1/5 and SNAIL levels in preeclamptic placentas. Mechanistically, we show that TGF{beta}1 induces transient SMAD1/5 phosphorylation via dual engagement of the TGF{beta} type I receptor ALK5 and the BMP type I receptor ALK2 in both HTR8/SVneo cells and human trophoblast stem cells. Moreover, single-nucleus transcriptomics of first-trimester placentas revealed co-expression of ACVR1, TGFBR1, SMAD1 and SMAD5 at the transition zone between cytotrophoblasts and extravillous trophoblasts. Our findings suggest that transient TGF{beta}-induced ALK5/ALK2-SMAD1/5 signaling is critical for EMT initiation, a prerequisite for proper placental differentiation.

molecular biology↗

bioRxiv2025

Impact of nephrotoxins and oxidants on survival and transport function of hiPSC-derived renal proximal tubular cells

Due to their role in excretion, renal proximal tubule cells are susceptible to damage by toxic metabolites and xenobiotics. The regenerative capacity of the kidney allows for the replacement of damaged cells, a process involving differentiation programs. However, kidney function tends to decline, suggesting that the replacement cells may not achieve full functionality. To understand possible causes of this decline, we investigated effects of nephrotoxins and oxidants on the differentiation of induced pluripotent stem cells (iPSC) into proximal tubular epithelial-like cells (PTELC). Proliferation, apoptosis, senescence and expression of oxidative defense genes were analyzed in iPSCs, differentiating and differentiated cells treated with cisplatin (CisPt, up to 45 {micro}M), cyclosporin A (CycA, up to 12 {micro}M) and the oxidants menadione (Mena, up to 50 {micro}M) and tert-butylhydroquinone (tBHQ, up to 50 {micro}M). We found that differentiating cells were most sensitive to oxidants and showed increased sensitivity to CisPt, whereas all differentiation stages showed similar sensitivity to CycA. Both oxidative stress and CisPt triggered apoptosis in all differentiation stages, whereas CycA mainly induced senescence. Treatment during differentiation resulted in long-term effects on gene expression in differentiated cells. While oxidants had no effect on transport function of differentiated cells, CisPt and CycA impaired albumin uptake. Our data suggest a substantial sensitivity of differentiating cells to nephrotoxins and oxidants, an aspect that could potentially interfere with regenerative processes.

pharmacology and toxicology↗

bioRxiv2024

Structural insights into the opening mechanism of C1C2 channelrhodopsin

Channelrhodopsins, light-gated cation channels, enable precise control of neural cell depolarization or hyperpolarization with light in the field of optogenetics. This study integrates time-resolved serial crystallography and atomistic molecular dynamics (MD) simulations to resolve the structural changes during C1C2 channelrhodopsin activation. Our observations reveal that within the crystal environment, C1C2 predominantly remains in a light-activated state with characteristics of the M390 intermediate. Here, rearrangement of retinal within its binding pocket partially opens the central gate towards the extracellular vestibule. These structural changes initiate channel opening but were insufficient to allow K+ flow. Adjusting protonation states to represent the subsequent N520 intermediate in our MD simulations induced further conformational changes, including rearrangements of transmembrane helices 2 and 7, that opened the putative ion- translocation pathway. This allows spontaneous but low cation but not anion conduction, that matches experiments. Our findings provide critical structural insights into key intermediates of the channel opening mechanism, enhancing our understanding of ion conduction and selectivity in channelrhodopsins at an atomistic level.

biophysics↗

bioRxiv2024

Two-Photon NAD(P)H-FLIM reveals unperturbed energy metabolism of Ascaris suum larvae, in contrast to host macrophages upon artemisinin derivatives exposure

Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections are common in co-endemic regions. Artemisinin derivatives (ARTs)--artesunate, artemether, and dihydroartemisinin--are standard malaria treatments and are also known to influence the energy metabolism of parasites, tumors, and immune cells. Herein, we explore the potential of ARTs to influence ascariasis either by directly affecting larvae or indirectly by modifying macrophage responses. Ascaris suum third-stage larvae and porcine IL-4 polarised (M2-like) macrophages were exposed to ARTs in vitro, and their metabolism was evaluated using two-photon NAD(P)H-FLIM. Both larvae and M2-like macrophages exhibited a steady-state bioenergetic profile of high oxidative phosphorylation and low anaerobic glycolysis. In A. suum larvae, two metabolically distinct regions were identified, with particularly high DUOX activity in the pharynx compared to the midgut. The metabolic profile of both larval regions were, however, unperturbed by ARTs exposure. In contrast, exposure of M2-like macrophages to ARTs induced a metabolic shift towards high anaerobic glycolysis and reduced metabolic activity, suggesting a possible indirect effect of ARTs on the helminth infection. Overall, two-photon NAD(P)H-FLIM proved to be a powerful tool for studying specific metabolic pathways in Ascaris larvae and host macrophages, offering valuable insights into the metabolic mechanisms of drug action on both parasite and host.

biophysics↗

bioRxiv2024

Anomalous diffusion analysis reveals cooperative locomotion of adult parasitic nematodes in sex-mixed groups.

Parasitic worms are widespread throughout the world and causing agents of chronic infections in humans and animals. The majority of these pathogens parasitize the gut of the infected hosts, however very little is known about the locomotion of the worms dwelling the gut. We studied the movement of Heligmosomoides bakeri (previously Heligmosomoides polygyrus), a natural infection of mice and usually used as animal model to study the roundworm infections. We investigated the locomotion of H. bakeri in simplified environments mimicking key physical features of the intestinal lumen, i.e. various medium viscosities, and a periodical intestinal villi topography. The non-periodical nematode motion in these settings could be described by anomalous diffusion theory. Fascinatingly, an oriented, super-diffusive locomotion of nematodes in sex-mixed groups were detected, in the sense of a cooperative, but not collective (swarm-like) migration stimulated by mating and reproduction, while individual nematodes moved randomly, following a diffusive motion regime. High mucus-like medium viscosity and villi topography, representing physical constraints of nematode locomotion, slowed down but did not prevent this cooperative migration. Additionally, the mean displacement rate of nematodes in sex-mixed groups of 6{middle dot}10-4 mm/s in viscous mucus-like medium are in good agreement with estimates of nematode migration velocities between 10-4 to 10-3 mm/s in the gut. Thus, our data indicate the intestinal nematodes motion to be non-periodic and random but triggered to be oriented by kin of the different sex.

biophysics↗

bioRxiv2024

Concurrent Ascaris infection modulates host immunity resulting in impaired control of Salmonella infection in pigs

Ascaris is one of the most widespread helminth infections of humans and pigs, leading to chronic morbidity in humans and considerable economic losses in pig farming. Additionally, pigs are an important reservoir for the zoonotic bacterial pathogen Salmonella, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. Ascaris-infected pigs exhibited numerous hallmarks of a type 2 immune response in organs impacted by larval migration, including increased Th2 cells, increased IL-4 production, eosinophilia, and increased expression of CD206, a marker for alternatively activated macrophages. While we observed only mild changes in frequencies of CD4+ Treg, Ascaris- infected pigs had increased frequencies of CD8+ Treg. We show that type 2 immune signals enhance susceptibility of macrophages to Salmonella infection in vitro. Furthermore, Ascaris impaired Salmonella-induced monocytosis and TNF- production by myeloid cells. Hence, our data demonstrate widespread immunomodulation during an acute Ascaris infection that facilitates the microbial spread into gut-associated lymphoid tissue in a Salmonella coinfection. ImportanceIn experimentally infected pigs we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity to render pigs more susceptible to invading Salmonella. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed a type 2 immune response to be induced during an Ascaris infection correlating with an increased susceptibility of pigs to the concurrent bacterial infection.

immunology↗

bioRxiv2022

A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma

SUMMARY PARAGRAPHDisease-causing mutations in genes encoding transcription factors (TFs) are a recurrent finding in hematopoietic malignancies and might involve key regulators of lineage adherence and cellular differentiation1-3. Such mutations can affect TF-interactions with their cognate DNA-binding motifs4, 5. Whether and how TF-mutations impact upon the nature of binding to TF composite elements (CE) and influence their interaction with other TFs is unclear. Here, we report a new mechanism of TF alteration in human lymphomas with perturbed B cell identity. It is caused by a recurrent somatic missense mutation c.295T>C (p.Cys99Arg; p.C99R) targeting the center of the DNA-binding domain of Interferon Regulatory Factor 4 (IRF4), a key TF in immune cell-differentiation and -activation6, 7. IRF4-C99R fundamentally alters IRF4 DNA-binding, with loss-of-binding to canonical IRF motifs and neomorphic gain-of-binding to canonical and non-canonical IRF composite elements (CEs). Furthermore, IRF4-C99R thoroughly modifies IRF4 function, by blocking IRF4-dependent plasma cell induction, and up-regulating disease-specific genes in a non-canonical Activator Protein-1 (AP-1)-IRF-CE (AICE)-dependent manner. Our data explain how a single arginine mutation creates a complex switch of TF specificity and gene regulation. These data open the possibility of designing specific inhibitors to block the neomorphic, disease-causing DNA-binding activities of a mutant transcription factor.

cancer biology↗

bioRxiv2022

STAT5 Gain-of-Function Variants Promote Precursor T-Cell Receptor Activation to Drive T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive immature T-cell cancer. Hotspot mutations in JAK-STAT pathway members IL7R, JAK1 and JAK3 were analyzed in depth. However, the role of STAT5A or STAT5B mutations promoting their hyperactivation is poorly understood in the context of T-cell cancer initiation and acute leukemia progression. Importantly, the driver mutation STAT5BN642H encodes the most frequent activating STAT5 variant in T-ALL associated with poor prognosis. Here, we show that hyperactive STAT5 promotes early T-cell progenitor (ETP)-ALL-like cancer in mice and upregulated genes involved in T-cell receptor signaling (TCR), even in absence of surface TCR promoting. Importantly, these genes were also overexpressed in human T-ALL and other STAT5-dependent T-cell cancers. Moreover, human T-ALL cells were sensitive to pharmacologic inhibition by dual STAT3/5 degraders or ZAP70 tyrosine kinase blockers. Thus, we define STAT5 target genes in T-ALL that promote pre-TCR signaling mimicry. We propose therapeutic targeting using selective ZAP70 or STAT3/5 inhibitors in a subgroup of T-ALL patients with prominent IL-7R-JAK1/3-STAT5 activity. SignificanceWe provide detailed functional characterizations of hyperactive STAT5A or STAT5B in thymic T-cell development and transformation. We found that hyperactive STAT5 transcribes T-cell-specific kinases or pre-TCR signaling hubs to promote T-ALL. Biomolecular and next-generation-sequencing methods, transgenesis and pharmacologic interference revealed that hyperactive STAT5 is a key oncogenic driver that can be targeted in T-ALL using STAT3/5 or SYK family member tyrosine kinase inhibitors. Conflict of interestThe authors declare no potential conflicts of interest.

cancer biology↗

bioRxiv2022

Population dynamics of free-roaming dogs in Europe and implications for population control

Changes in free-roaming dog population size are important indicators of the effectiveness of dog population management. Assessing the effectiveness of different management methods also requires estimating the processes that change population size, such as the rates of recruitment into and removal from a population. This is one of the first studies to quantify the size, rates of recruitment and removal, and health and welfare status of free-roaming dog populations in Europe. We determined the size, dynamics, and health status of free-roaming dog populations in Pescara, Italy, and Lviv, Ukraine, over a 15-month study period. Both study populations had ongoing dog population management through catch-neuter-release and sheltering programmes. Average monthly apparent survival probability was 0.93 (95% CI 0.81-1.00) in Pescara and 0.93 (95% CI 0.84-0.99) in Lviv. An average of 7 dogs km-2 were observed in Pescara and 40 dogs km-2 in Lviv. Per capita entry probabilities varied between 0.09 and 0.20 in Pescara, and 0.12 and 0.42 in Lviv. In Lviv, detection probability was lower on weekdays (odds ratio: 0.74, 95% CI 0.53-0.96) and higher on market days (odds ratio: 2.58, 95% CI 1.28-4.14), and apparent survival probability was lower in males (odds ratio: 0.25, 95% CI 0.03-0.59). Few juveniles were observed in the study populations, indicating that recruitment may be occurring by movement between dog subpopulations (e.g. from local owned or neighbouring free-roaming dog populations), with important consequences for population control. This study provides important data for planning effective dog population management and for informing population and infectious disease modelling. The results emphasise the importance of dog population management efforts that encourage responsible ownership through reduced abandonment and cover the entire city to reduce the risk of dog movement between sections of the city hindering management efforts.

ecology↗

bioRxiv2022

Structure and Protein-Protein Interactions of Ice Nucleation Proteins Drive Their Activity

ABSTRACTMicrobially-produced ice nucleating proteins (INpro) are unique molecular structures with the highest known catalytic efficiency for ice formation. Their critical role in rain formation and frost damage of crops together with their diverse commercial applications warrant an in-depth under-standing of their inherent ice nucleation mechanism. We used the machine-learning based software Al-phaFold to develop the first ab initio structural model of a bacterial INpro which is a novel beta-helix structure consisting of repeated stacks of two beta strands connected by two sharp turns. Using the synchrotron radiation circular dichroism, we validated the {beta}-strand content of the model. Combining functional studies of purified recombinant INpro, electron microscopy and modeling, we further demonstrate that the formation of dimers and higher-order oligomers is key to INpro activity. This work presents a major advance in understanding the molecular foundation for bacterial ice-nucleation activity and the basis for investigating the mechanistic role of INpro-induced ice formation in the atmosphere, and for commercial design and production of ice-nucleating particles for industrial applications.

microbiology↗

bioRxiv2021

Assessing the impact of free-roaming dog population management through systems modelling

Free-roaming dogs can present significant challenges to public health, wildlife conservation, and livestock production. Their own welfare may also be a concern, as free-roaming dogs can experience poor health and welfare. Dog population management is widely conducted to mitigate these issues. To ensure efficient use of resources, it is critical that effective, cost-efficient, and high-welfare strategies are identified. The dog population comprises distinct subpopulations characterised by their restriction status and level of ownership, but the assessment of dog population management often fails to consider the impact of the interaction between subpopulations on management success. We present a system dynamics model that incorporates an interactive and dynamic system of dog subpopulations. We identify that methods incorporating both fertility control and responsible ownership interventions (a reduction in abandonment and an increase in shelter adoptions) have the greatest potential to reduce free-roaming dog population sizes over longer periods of time, whilst being cost-effective and improving overall welfare. We suggest that future management should be applied at high levels of coverage and should target all sources of population increase, such as abandonment, births, and free-roaming owned dogs, to ensure effective and cost-efficient reduction in free-roaming dog numbers.

zoology↗

bioRxiv2021

A semisynthetic glycoconjugate provides expanded cross-serotype protection against Streptococcus pneumoniae

Streptococcus pneumoniae infections are the leading cause of child mortality globally. Current vaccines fail to induce a protective immune response towards a conserved part of the pathogen, resulting in new serotypes causing disease. Therefore, new vaccine strategies are urgently needed. Described is a two-pronged approach combining S.pneumoniae proteins, pneumolysin and PspA, with a precisely defined synthetic oligosaccharide, whereby the carrier protein acts as a serotype-independent antigen to provide additional protection. Proof of concept in mice and swine models revealed that the conjugates inhibit colonization of the nasopharynx, decrease the bacterial load and reduce disease severity in the bacteria challenged model. Immunization of piglets provided the first evidence for the immunogenicity and protective potential of synthetic glycoconjugate vaccine in a large animal model. A combination of synthetic oligosaccharides with proteins from the target pathogen opens the path to create broadly cross-protective ("universal") pneumococcal vaccines.

immunology↗