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bioRxiv2018

TRAF6 directs Foxp3 localization and facilitates Treg function through K63-type ubiquitination

Regulatory T cells (Treg) are crucial mediators of immune control. The characteristic gene expression and suppressive function of Treg depend considerably on the stable expression and activity of the transcription factor Foxp3. While transcriptional regulation of the Foxp3 gene has been studied in depth, both the expression and function of Foxp3 are also modulated at the protein level. However, the molecular players involved in posttranslational Foxp3 regulation are just beginning to be elucidated. Here we found TRAF6-deficient Tregs were dysfunctional in vivo; mice with Treg-restricted deletion of TRAF6 were resistant to B16 melanomas and displayed enhanced anti-tumor immunity. We further determined that Foxp3 undergoes lysine-63 chain (K63) ubiquitination at lysine 262 mediated by the E3 ligase TRAF6. When deprived of TRAF6 activity or rendered insensitive to K63 ubiquitination, Foxp3 displayed aberrant, perinuclear accumulation, disrupted function. Thus, Foxp3 ubiquitination by TRAF6 ensures proper localization of Foxp3 and facilitates Foxp3s gene-regulating activity in Tregs. These results implicate TRAF6 as a key posttranslational, Treg-stabilizing force that may be targeted in novel tolerance-breaking therapies.

immunology↗

bioRxiv2018

Observed Antibody Space: a resource for data mining next generation sequencing antibody repertoires

Antibodies are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made antibodies the primary class of biopharmaceuticals. Recently it has become possible to query their immense natural diversity using next-generation sequencing of immunoglobulin gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 53 studies, covering more than half a billion antibody sequences across diverse immune states, organisms and individuals. We have sorted, cleaned, annotated, translated and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at antibodymap.org. The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.

immunology↗

bioRxiv2018

The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. In IgAN, immune complex deposite in glomerular mesangium, which induce inflammation and affect the kidneys normal functions. However, the exact pathogenesis of IgAN is still incompletely understood. Further, in current practice the clinical diagnosis relies on needle biopsy on renal tissue. Therefore, a non-invasive method for clinical diagnosis and prognosis surveillance of the disease is in high demand. In this paper, we investigated both the T cell receptor bata chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire of kidney infiltrating and circulating lymphocytes of IgAN patients by immune repertoire high throughput sequencing. We found that the features of TCRB and IGH in the renal tissues were remarkably different from that in blood, including a decreased repertoire diversity and increased IgA and IgG frequency, and more activated B cells. The CDR3 length of PBMC TCRB and IGH in patients is significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clone selection. We also found that the IgA1 frequency in the PBMC of IgAN is significant higher than that in other Nephropathy (NIgAN) and healthy control, which is consistent with the previous reports on the level of IgA1 producing B cells and serum IgA1. Significantly, we identified a set of IgAN disease related TCRB and IGH CDR3s, which can be used to distinguish IgAN from NIgAN and healthy controls from the blood with high accuracy. These results indicated that TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for IgAN diagnosis. The characteristics of kidney infiltrating and circulating lymphocytes repertoire shed light on IgAN detection, treatment and surveillance.

immunology↗

bioRxiv2018

Global landscape of mouse and human cytokine transcriptional regulation

Cytokines play a central role in immune development, pathogen responses, and diseases. Cytokines are highly regulated at the transcriptional level by combinations of transcription factors (TFs) that recruit cofactors and the transcriptional machinery. Here, we review three decades of studies to generate a comprehensive database reporting 843 and 647 interactions between TFs and cytokines genes, in human and mouse respectively (http://cytreg.bu.edu). We provide a historic perspective on cytokine regulation discussing research trends and biases. More importantly, by integrating this comprehensive database with other functional datasets, we determine general principles governing the transcriptional regulation of cytokine genes. In particular, we show a correlation between TF connectivity and immune phenotype and disease, we discuss the balance between tissue-specific and pathogen-activated TFs regulating each cytokine gene, and cooperativity and plasticity in cytokine regulation. Finally, we illustrate the use of our database as a blueprint to study TF-cytokine regulatory axes in autoimmune diseases.

immunology↗

bioRxiv2018

N-terminal degradation activates the Nlrp1b inflammasome

Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptotic cell death. The anthrax lethal factor metalloprotease and small molecule DPP8/9 inhibitors both activate the Nlrp1b inflammasome, but the molecular mechanism of Nlrp1b activation is not known. Here, we used genome-wide CRISPR/Cas9 knockout screens to identify genes required for Nlrp1b-mediated pyroptosis, and discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves Nlrp1b, which induces the N-end rule-mediated degradation of the Nlrp1b N-terminus and thereby frees the Nlrp1b C-terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the Nlrp1b N-terminus, but, in contrast, not through the N-end rule pathway. Overall, these data reveal that N-terminal degradation is the common mechanism for activation of this innate immune sensor protein.\n\nOne Sentence SummaryProteasome-mediated degradation of the Nlrp1b N-terminus releases the Nlrp1b C-terminus to activate caspase-1 and induce pyroptotic cell death.

immunology↗

bioRxiv2018

Functional degradation: a mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes

Inflammasomes are multi-protein platforms that initiate innate immunity by recruitment and activation of Caspase-1. The NLRP1B inflammasome is activated upon direct cleavage by the anthrax lethal toxin protease. However, the mechanism by which cleavage results in NLRP1B activation is unknown. Here we find that cleavage results in proteasome-mediated degradation of the N-terminal domains of NLRP1B, liberating a C-terminal fragment that is a potent Caspase-1 activator. Proteasome-mediated degradation of NLRP1B is both necessary and sufficient for NLRP1B activation. Consistent with our new functional degradation model, we identify IpaH7.8, a Shigella flexneri ubiquitin ligase secreted effector, as an enzyme that induces NLRP1B degradation and activation. Our results provide a unified mechanism for NLRP1B activation by diverse pathogen-encoded enzymatic activities.\n\nOne Sentence SummaryTwo distinct pathogen enzymes activate an innate immune sensor called NLRP1B by a mechanism that requires proteasome-mediated degradation of NLRP1B.

immunology↗

bioRxiv2018

Mycobacterium marinum infection drives foam cell differentiation in zebrafish infection models

Host lipid metabolism is an important target for subversion by pathogenic mycobacteria such as Mycobacterium tuberculosis. The appearance of foam cells within the granuloma are well-characterised effects of chronic tuberculosis. The zebrafish-Mycobacterium marinum infection model recapitulates many aspects of human-M. tuberculosis infection and is used as a model to investigate the structural components of the mycobacterial granuloma. Here, we demonstrate that the zebrafish-M. marinum granuloma contains foam cells and that the transdifferentiation of macrophages into foam cells is driven by the mycobacterial ESX1 pathogenicity locus. This report demonstrates conservation of an important aspect of mycobacterial infection across species.

immunology↗

bioRxiv2018

Identification of a host collagen inducing factor from the excretory secretory proteins of Trichinella spiralis using immunoscreening

BackgroundIn a previous study, we found that Trichinella spiralis excretory and secretory proteins (ES-P) most likely activate collagen synthesis via TGF-{beta}/Smad signaling, and this event could influence collagen capsule formation.\n\nMethodology/Principal FindingsIn order to identify the specific collagen inducing factor, ES-P was fractionated by a Superdex 200 10/300 GL column. We obtained three large fractions, F1, F2, and F3, but only F3 had collagen gene inducing ability. After immunoscreening, 10 collagen inducing factor candidates were identified. Among them, TS 15-1 and TS 15-2 were identical to the putative trypsin of T. spiralis. The deduced TS 15-1 (M.W. = 72 kDa) had two conserved catalytic motifs, an N-terminal Tryp_SPc domain (TS 15- 1n) and a C-terminal Tryp_SPc domain (TS 15-1c). To determine their collagen inducing ability, recombinant proteins (rTS 15-1n and rTS 15-1c) were produced using the pET-28a expression system. TS 15-1 is highly expressed during the muscle larval stage and has strong antigenicity. We determined that rTS 15-1c could elevate collagen I via activation of the TGF-{beta}1 signaling pathway in vitro and in vivo.\n\nConclusion/SignificanceIn conclusion, we identified a host collagen inducing factor from T. spiralis ES-P using immunoscreening and demonstrated its molecular characteristics and functions.\n\nAuthor SummaryTrichinella spiralis can make collagen capsules in host muscle cells during its life cycle, which encapsulates muscle stage larvae. Many investigators have tried to reveal the complex mechanism behind this collagen capsule architecture, and it has been suggested that several serine proteases in excretory-secretory proteins of the parasite are potential collagen capsule inducing factors. In addition, collagen synthesis is activated through the TGF-{beta}/Smad signaling pathway and these events are closely related with protease activated receptor 2 which was activated by various serine proteases. In this study, we isolated and characterized a collagen gene expression inducer from T. spiralis ES-P using immunoscreening and investigated the candidate protein for its usefulness as a wound healing therapeutic agent.

immunology↗

bioRxiv2018

Baculovirus-inducing fast-acting innate immunity kills Plasmodium liver stages

Baculovirus (BV), an enveloped insect virus with a circular double-stranded DNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. Here, we show that BV administration not only sterilely protects BALB/c mice for at least 7 days from subsequent Plasmodium berghei sporozoite infection but also eliminates existing liver-stage parasites completely, effects superior to those of primaquine, and does so in a TLR9-independent manner. Six hours post-BV administration, IFN- and IFN-{gamma} were robustly produced in serum, and RNA transcripts of interferon-stimulated genes were drastically upregulated in the liver. The in vivo passive transfer of post-BV administration serum effectively eliminated liver-stage parasites, and IFN- neutralization abolished this effect, indicating that the BV liver-stage parasite killing mechanism is downstream of the type I IFN signaling pathway. Our results demonstrate that BV is a potent IFN-inducing prophylactic and therapeutic agent with great potential for further development as a new malaria vaccine and/or anti-hypnozoite drug.

immunology↗

bioRxiv2018

A hypothetical new role for single-stranded DNA binding proteins in the immune system

The breadth of the host range of single-stranded DNA (ssDNA) viruses is roughly comparable to the host range of double-stranded DNA viruses (dsDNA). Yet, general ssDNA sensing receptors that activate the immune system have not been unequivocally identified while numerous dsDNA sensing receptors are known. Here, we hypothesize that some of the Single-Stranded DNA Binding (SSB) proteins may act as receptors that detect single-stranded DNA from pathogens and activate the innate immune system. As the first test of our hypothesis, we checked whether human genes that are known to bind to ssDNA are potentially interferon-regulated. Out of the 102 human genes that are known to have ssDNA binding ability 23 genes show a more than two-fold increase in gene expression upon interferon treatment. Single-stranded DNA viruses are pathogens of not only animals but also of plants and protozoans. We used this information to further prioritize our candidate list to ssDNA binding genes that are common between the model plant Arabidopsis thaliana and humans. Based on these strategies, we shortlist several promising candidate genes including the HMGB1 gene which could act as a ssDNA sensor that activates the immune system. Agreeably though we cannot establish a definitive role for these genes as ssDNA sensors of the immune system as yet, our preliminary analysis suggests the potential existence of ssDNA binding protein-like receptors (SLRs) that are worth investigating further.

immunology↗

bioRxiv2018

High throughput single cell sequencing of both T-cell-receptor-beta alleles

Allelic exclusion is a vital mechanism for the generation of monospecificity to foreign antigens in B- and T-lymphocytes. Here we developed a high-throughput barcoded method to simultaneously analyze the VDJ recombination status of both mouse T cell receptor beta alleles in hundreds of single cells using Next Generation Sequencing.

immunology↗

bioRxiv2018

Acute-phase CD4+ T cell responses targeting invariant viral regions are associated with control of live-attenuated simian immunodeficiency virus

We manipulated SIVmac239{Delta}nef, a model of MHC-independent viral control, to evaluate characteristics of effective cellular responses mounted by Mauritian cynomolgus macaques (MCMs) who express the M3 MHC haplotype that has been associated with poor control of pathogenic SIV. We created SIV{Delta}nef-8x to test the hypothesis that effective SIV-specific T cell responses targeting invariant viral regions can emerge in the absence of immunodominant CD8+ T cell responses targeting variable epitopes, and that control is achievable in individuals lacking known protective MHC alleles. Full proteome IFN{gamma} ELISPOT assays identified six newly targeted immunogenic regions following SIV{Delta}nef-8x infection of M3/M3 MCMs. We deep sequenced circulating virus and found that four of the six newly targeted regions rarely accumulated mutations. Six animals infected with SIV{Delta}nef-8x targeted at least one of the four invariant regions and had a lower set point viral load compared to two animals that did not target any invariant regions. We found that MHC class II molecules restricted all four of the invariant peptide regions, while the two variable regions were restricted by MHC class I molecules. Therefore, in the absence of immunodominant CD8+ T cell responses that target variable regions during SIVmac239{Delta}nef infection, individuals without protective MHC alleles developed predominantly CD4+ T cell responses specific for invariant regions that may improve control of virus replication. Our results provide some evidence that antiviral CD4+ T cells during acute SIV infection can contribute to effective viral control and should be considered in strategies to combat HIV infection.\n\nImportanceStudies defining effective cellular immune responses to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have largely focused on a rare population that express specific MHC class I alleles and control virus replication in the absence of antiretroviral treatment. This leaves in question whether similar effective immune responses can be achieved in the larger population. The majority of HIV-infected individuals mount CD8+ T cell responses that target variable viral regions that accumulate high-frequency escape mutations. Limiting T cell responses to these variable regions and targeting invariant viral regions, similar to observations in rare elite controllers, may provide an ideal strategy for the development of effective T cell responses in individuals with diverse MHC genetics. Therefore, it is paramount to determine whether T cell responses can be redirected towards invariant viral regions in individuals without protective MHC alleles and if these responses improve control of virus replication.

immunology↗

bioRxiv2018

TRAIL (CD253) Sensitizes Human Airway Epithelial Cells to Toxin-Induced Cell Death

Inhalation of ricin toxin is associated with the onset of acute respiratory distress syndrome (ARDS), characterized by hemorrhage, inflammatory exudates, and tissue edema, as well as the near complete destruction of the lung epithelium. Here we report that the Calu-3 human airway epithelial cell line is relatively impervious to the effects of ricin, with little evidence of cell death even upon exposure to microgram amounts of toxin. However, the addition of exogenous soluble TNF-Related Apoptosis Inducing Ligand (TRAIL; CD253) dramatically sensitized Calu-3 cells to ricin-induced apoptosis. Calu-3 cell killing in response to ricin and TRAIL was reduced upon the addition of caspase-8 and caspase-3/7 inhibitors, but not caspase 9 inhibitors, consistent with involvement of extrinsic apoptotic pathways in cell death. We employed nCounter Technology to define the transcriptional response of Calu-3 cells to ricin, TRAIL, and the combination of ricin plus TRAIL. An array of genes associated with inflammation-and cell death were significantly up regulated upon treatment with ricin toxin, and further amplified upon addition of TRAIL. Of particular note was IL-6, whose expression in Calu-3 cells increased 300-fold upon ricin treatment and more than 750-fold upon ricin and TRAIL treatment. IL-6 secretion by Calu-3 cells was confirmed by cytometric bead array. Based on these finding, we speculate that the severe airway epithelial cell damage observed in animal models following ricin exposure is a result of a positive feedback loop driven by pro-inflammatory cytokines like TRAIL and IL-6.

immunology↗

bioRxiv2018

Clinical scoring is the most sensitive biomarker detecting developing sepsis in newborn mice

Newborn individuals are highly susceptible to infectious diseases. For better insights into age-specific host-pathogen interactions infection models are increasingly employed in neonatal mice. However, for newborn mice no measures are available to objectify the clinical disease state, particularly not in a longitudinal manner, to meet legal animal welfare requirements. We developed a scoring system for newborn mice that relies on observational and examination-based parameters and validated it by applying a Staphylococcus aureus-induced infection model in two different mouse strains.\n\nThe scoring results strongly correlated with the death kinetics independent of which mouse strain was used. A score above 7 predicted fatality. While the score values increased already at early sepsis stages the large majority of plasma cytokine levels remained comparable to those in uninfected control neonates. The levels of interleukin (Il)-6, chemokine C-C motif ligand 5, Il-1 and tumor necrosis factor were not increased before 24 hours after infection and correlated only at this late stage of sepsis with the scored disease state.\n\nWe propose the first clinical scoring system that serves as important research tool to evaluate the clinical course of sepsis in newborn mice. It detects health impairments of newborn pups in a highly sensitive and longitudinal manner, providing information about the disease severity as well as prognosis.

immunology↗

bioRxiv2018

White spot syndrome virus infection induces Caspase 1-mediated antiviral cell death in crustacean

In vertebrates, pyroptosis is an intensely inflammatory form of programmed cell death which is dependent on Caspase 1 activation and release of cytoplasmic cytokines including IL-1{beta}. This death pathway is critical for controlling pathogenic infection by mobilizing immune cells and stimulating the development of adaptive immune response. In invertebrates, however, due to the lack of adaptive immune response, it is still elusive whether Caspase 1-dependent cell death pathway exists. In this study, our data showed that Caspase 1-mediated cell death was activated by white spot syndrome virus (WSSV) infection to control the virus in shrimp. Caspase 1 had a higher expression level in hemocytes and lymphoid-like organ in shrimp and WSSV infection was significantly promoted upon the inhibition of Caspase 1 enzymatic activity. IL-1{beta}-like protein was identified as the substrate of Caspase 1 and its interaction with Caspase 1 was validated ectopically and endogenously. Moreover, IL-1{beta} like protein was released into extracellular contents under WSSV infection and Prophenoloxidase system was activated, resulting in the reduction of WSSV copies in vivo. Our data unraveled a previously unidentified mechanism through which Caspase 1-dependent cell death controlled virus infection in shrimp. Therefore, our study opened the possibility that an invertebrate cytokine network might be operative and regulate host defenses against virus infection as in vertebrates.\n\nAuthor SummaryThe elimination of infected cells by programmed cell death is considered as one of the most important anti-pathogen responses. Pyroptosis is one form of programmed cell death, which is mediated by Caspase 1 activation. Activated Caspase 1 can process the inactive precursors of interleukin 1{beta} (IL-1{beta}) into mature inflammatory cytokines to induce potent immune responses. Meanwhile, pyroptosis also induces morphologic changes, DNA fragmentation and chromatin condensation to destroy infected cells. However, due to the lack of efficient adaptive immune responses, it is still unclear whether Caspase 1-mediated cell death also exits and plays such an important role in defending hosts from pathogen invasion in invertebrates. In our data, Caspase 1 gene was characterized and Caspase 1-mediated cell death pathway was validated in shrimp. The Caspase 1-mediated cell death pathway was enhanced by white spot syndrome virus (WSSV) infection to control the virus in shrimp. IL-1{beta}-like protein was cleaved by Caspase 1 and released into extracellular contents under WSSV infection to activate Prophenoloxidase system, leading to the reduction of WSSV copies in shrimp in vivo. On the other hand, silencing of Caspase 1 or IL-1{beta}-like gene facilitated virus infection in shrimp. Our study indicated that Casapase-1-mediated cell death played an important antiviral role in shrimp against WSSV infection and opened the possibility that an invertebrate cytokine network might be operative.

immunology↗

bioRxiv2018

Hyd ubiquitinates the NF-κB co-factor Akirin to activate an effective immune response in Drosophila

One Sentence SummaryUpon microbial infection in Drosophila, the E3-ubiquitin ligase Hyd ubiquitinylates the NF-{kappa}B co-factor Akirin for its efficient binding to the NF-{kappa}B factor Relish and subsequent activation of immune effectors genes.\n\nABSTRACTThe Drosophila IMD pathway is activated upon microbial challenge with Gramnegative bacteria to trigger the innate immune response. In order to decipher this NF-{kappa}B signaling pathway, we undertook an ex-vivo RNAi screen targeting specifically E3 ubiquitin ligases and identified the HECT E3 ubiquitin ligase Hyperplastic Discs \"Hyd\" as a new actor of the IMD pathway. We showed that Hyd targets the NF-{kappa}B cofactor of Akirin. The K63-polyubiquitination chains deposited by Hyd decorate Akirin for its efficient binding to the NF-{kappa}B transcription factor Relish. We showed that this Hyd-mediated interaction is critical to activate immune-induced genes that depend on both Relish and Akirin, but is dispensable for those that depend solely on Relish. Therefore Hyd is key in operating a NF-{kappa}B transcriptional selectivity downstream of the IMD pathway. Drosophila depleted for Hyd or Akirin failed to express the full set of immune-induced anti-microbial peptide coding genes and succumbed to immune challenges. We showed further that Ubr5, the mammalian homolog of Hyd, is also required downstream of the NF-{kappa}B pathway for the IL1{beta}-mediated IL6 activation. This study links the action of a E3-ubiquitin ligase to the activation of immune effector genes, deepening our understanding of the involvement of ubiquitination in inflammation and identifying a potential target for the control of inflammatory diseases.

immunology↗

bioRxiv2018

Organized spatial patterns of activated β2 integrins in arresting neutrophils

The transition from leukocyte rolling to firm adhesion is called arrest. {beta}2 integrins are required for neutrophil arrest1. Chemokines can trigger neutrophil arrest in vivo2 and in vitro3. Resting integrins4 exist in a \"bent-closed\" conformation, i.e., not extended (E-) and not high affinity (H-), unable to bind ligand. Electron microscopic images of isolated {beta}2 integrins in \"open\" and \"closed\" conformations5 inspired the switchblade model of integrin activation from E-H- to E+H- to E+H+67. Recently8, we discovered an alternative pathway of integrin activation from E-H- to E-H+ to E+H+. Spatial patterning of activated integrins is thought to be required for effective arrest, but so far only diffraction-limited localization maps of activated integrins exist8. Here, we combine superresolution microscopy with molecular modeling to identify the molecular patterns of H+E-, H-E+, and H+E+ activated integrins on primary human neutrophils. At the time of neutrophil arrest, E+H+ integrins form oriented (non-random) nanoclusters that contain a total of 4,625{+/-}369 E+H+ {beta}2 integrin molecules.

immunology↗

bioRxiv2018

Human Als3p Antibodies are Surrogate Markers of NDV-3A Vaccine Efficacy Against Recurrent Vulvovaginal Candidiasis

A Phase 1b/2a clinical trial of NDV-3A vaccine containing a Candida albicans recombinant Als3 protein protected women <40 years old from recurrent vulvovaginal candidiasis (RVVC). We investigated the potential use of anti-Als3p sera as surrogate marker of NDV-3A efficacy. Pre- and post-vaccination sera from subjects who experienced recurrence of VVC (R) versus those who were recurrence-free (non-recurrent, NR) were evaluated. Anti-Als3p antisera obtained were evaluated for; 1) titer and subclass profile; 2) their ability to influence C. albicans virulence traits including hyphal elongation, adherence to plastic, invasion of vaginal epithelial cells, biofilm formation on plastic and catheter material, and susceptibility to neutrophil killing in vitro. Serum IgG titers in NR patients were consistently higher than in R patients, particularly for anti-Als3 subclass IgG2. Sera from vaccinated NR patients reduced hyphal elongation, adhesion to plastic, invasion of vaginal epithelial cells and biofilm formation significantly more than pre-immune sera, or sera from R- or placebo-group subjects. Pre-adsorption of sera with C. albicans germ tubes eliminated these effects, while heat inactivation did not. Finally, sera from NR subjects enhanced neutrophil-mediated killing of C. albicans relative to pre-immune sera or sera from R patients. Our results suggest that higher Als3p antibody titers are associated with protection from RVVC, attenuate C. albicans virulence and augment immune clearance of the fungus in vitro. Thus, Als3p serum IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated with NDV-3A.\n\nAbbreviations

immunology↗