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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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At least 271 records · Page 15Linked to original sources

bioRxiv2017

Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys

Human cytomegalovirus (HCMV) is the most common congenital infection and a known cause of microcephaly, sensorineural hearing loss, and cognitive impairment among newborns worldwide. Natural maternal HCMV immunity reduces the incidence of congenital infection, but does not prevent the disease altogether. We employed a nonhuman primate model of congenital CMV infection to investigate the ability of preexisting antibodies to protect against placental CMV transmission. Pregnant, CD4+ T cell-depleted, rhesus CMV (RhCMV)-seronegative rhesus monkeys were treated with either standardly-produced hyperimmune globulin (HIG) from RhCMV-seropositive macaques or dose-optimized, potently RhCMV-neutralizing HIG prior to intravenous challenge with an RhCMV swarm. HIG passive infusion provided complete protection against fetal loss in both groups, and the potently-neutralizing HIG additionally inhibited placental transmission of RhCMV. Our findings suggest that antibody alone at the time of primary infection can prevent congenital CMV and therefore could be a primary target of vaccines to eliminate this neonatal infection.

immunology↗

bioRxiv2017

Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist

The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation.

immunology↗

bioRxiv2017

Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection

Approximately three quarters of acute HCV infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using Immunochip in European and African ancestries. We confirmed two previously reported significant associations, in the IL28B/IFNL41,2 and MHC regions, with spontaneous clearance in the European population. We further fine-mapped the MHC association to a region of about 50 kilo base pairs, down from 1 mega base pairs in the previous study. Additional analyses suggested that the association in the MHC locus might be significantly stronger for virus subtype 1a than 1b, suggesting that viral subtype may have influenced the genetic mechanism underlying the clearance of HCV.

immunology↗

bioRxiv2017

Mycophenolate mofetil increases susceptibility toopportunistic fungal infection independent of lymphocytes

Anti-proliferative agents that target lymphoid cells are common immunosuppressive agents used in the treatment of diverse autoimmune, graft versus host and inflammatory diseases. Mycophenolate mofetil (MMF) is an anti-proliferative agent that targets lymphoid dependence on inosine monophosphate dehydrogenase for the de novo purine synthesis of deoxyguanosine triphosphate (dGTP) for DNA replication. Here we show that MMF has a distinct and specific in vivo effect on macrophages, in the absence of lymphoid cells. This results in increased macrophage cell death that is dependent on the depletion of cellular GTP, independent of DNA synthesis. Furthermore, the macrophage specific effect of MMF treatment causes an increase in susceptibility to the opportunistic fungal infection Cryptococcus neoformans by reducing phagocytosis and increasing the release of intracellular pathogens via macrophage lysis. Our study demonstrates the need for a better mechanistic understanding of immunosuppressive treatments used in clinical practice and of the specific infection risks associated with certain treatment regimens.

immunology↗

bioRxiv2017

High-Risk Human Papillomavirus E7 Alters Host DNA Methylome And Represses HLA-E Expression In Human Keratinocytes

Human papillomavirus (HPV) infection distinctly alters methylation patterns in HPV-associated cancer. We have recently reported that HPV E7-dependent promoter hypermethylation leads to downregulation of the chemokine CXCL14 and suppression of antitumor immune responses. To investigate the extent of gene expression dysregulated by HPV E7-induced DNA methylation, we analyzed parallel global gene expression and DNA methylation using normal immortalized keratinocyte lines, NIKS, NIKS-16, NIKS-18, and NIKS-16{Delta}E7. We show that expression of the MHC class I genes is downregulated in HPV-positive keratinocytes in an E7-dependent manner. Methylome analysis revealed hypermethylation at a distal CpG island (CGI) near the HLA-E gene in NIKS-16 cells compared to either NIKS cells or NIKS-16{Delta}E7 cells, which lack E7 expression. The HLA-E CGI functions as an active promoter element which is dramatically repressed by DNA methylation. HLA-E protein expression on cell surface is downregulated by high-risk HPV16 and HPV18 E7 expression, but not by low-risk HPV6 and HPV11 E7 expression. Conversely, demethylation at the HLA-E CGI restores HLA-E protein expression in HPV-positive keratinocytes. Because HLA-E plays an important role in antiviral immunity by regulating natural killer and CD8+ T cells, epigenetic downregulation of HLA-E by high-risk HPV E7 may contribute to virus-induced immune evasion during HPV persistence.

immunology↗

bioRxiv2017

Cells With Treg-Specific FOXP3 Demethylation But Low CD25 Are Prevalent In Autoimmunity

Identification of alterations in the cellular composition of the human immune system is key to understanding the autoimmune process. Recently, a subset of FOXP3+ cells with low CD25 expression was found to be increased in peripheral blood from systemic lupus erythematosus (SLE) patients, although its functional significance remains controversial. Here we find in comparisons with healthy donors that the frequency of FOXP3+ cells within CD127lowCD25low CD4+ T cells (here defined as CD25lowFOXP3+ T cells) is increased in patients affected by autoimmune disease of varying severity, from combined immunodeficiency with active autoimmunity, SLE to type 1 diabetes. We show that CD25lowFOXP3+ T cells share phenotypic features resembling conventional CD127lowCD25highFOXP3+ Tregs, including demethylation of the Treg-specific epigenetic control region in FOXP3 that is highly enriched in HELIOS+ cells, and lack of IL-2 production. As compared to conventional Tregs, more CD25lowFOXP3+HELIOS+ T cells are in cell cycle (33.0% vs 20.7% Ki-67+; P = 1.3 x 10-9) and express the late-stage inhibitory receptor PD-1 (67.2% vs 35.5%; P = 4.0 x 10-18), while having reduced expression of the early-stage inhibitory receptor CTLA-4, as well as other Treg markers, such as FOXP3 and CD15s. The number of CD25lowFOXP3+ T cells are highly correlated (P = 1.2 x 10-19) with the proportion of CD25highFOXP3+ T cells in cell cycle (Ki-67+). These findings suggest that CD25lowFOXP3+ T cells represent a subset of Tregs that are derived from CD25highFOXP3+ T cells, and are a peripheral marker of recent Treg expansion in response to an autoimmune reaction in tissues.\n\nHighlights- FOXP3+ compartment within CD127lowCD25low T cells is expanded in autoimmune patients.\n\n- Increased numbers of CD25lowFOXP3+ T cells are a circulating marker of autoimmunity.\n\n- CD25lowFOXP3+ HELIOS+ T cells are fully demethylated at the FOXP3 TSDR.\n\n- CD25lowFOXP3+ T cells could represent a terminal stage of regulatory T cells.

immunology↗

bioRxiv2017

Tumor-infiltrating immune repertoires captured by single-cell barcoding in emulsion

Tumor-infiltrating lymphocytes (TILs) are critical to anti-cancer immune responses, but their diverse phenotypes and functions remain poorly understood and challenging to study. We therefore developed a single-cell barcoding technology for deep characterization of TILs without the need for cell-sorting or culture. Our emulsion-based method captures full-length, natively paired B-cell and T-cell receptor (BCR and TCR) sequences from lymphocytes among millions of input cells. We validated the method with 3 million B-cells from healthy human blood and 350,000 B-cells from an HIV elite controller, before processing 400,000 cells from an unsorted dissociated ovarian adenocarcinoma and recovering paired BCRs and TCRs from over 11,000 TILs. We then extended the barcoding method to detect DNA-labeled antibodies, allowing ultra-high throughput, simultaneous protein detection and RNA sequencing from single cells.

immunology↗

bioRxiv2017

Dynamics Of The Human Antibody Repertoire Following B-cell Depletion In Systemic Sclerosis

Systemic sclerosis with pulmonary arterial hypertension (SSc-PAH) is a debilitating and frequently lethal disease of unknown cause lacking effective treatment options. Lymphocyte anomalies and autoantibodies observed in systemic sclerosis have suggested an autoimmune character. Here we study the clonal structure of the B-cell repertoire in SSc-PAH using immunoglobulin heavy-chain sequencing before and after B-cell depletion. We found SSc-PAH to be associated with anomalies in B-cell development, namely altered VDJ rearrangement frequencies (reduced IGHV2-5 segment usage) and an increased somatic mutation-fixation probability in expanded B-cell lineages. SSc-PAH was also characterized by anomalies in B-cell homeostasis, namely an expanded IgD+ proportion with reduced mutation loads and an expanded proportion of highly antibody-secreting cells. Disease signatures pertaining to IGHV2-5 segment usage, IgD proportions and mutation loads were temporarily reversed after B-cell depletion. Analyzing the time course of B-cell depletion, we find that the kinetics of naive replenishment are predictable from baseline measurements alone, that release of plasma cells into the periphery can precede naive replenishment and that modes of B-cell receptor diversity are highly elastic. Our findings shed light on the humoral immune basis of SSc-PAH and provide insights into the effect of B-cell depletion on the antibody repertoire.\n\nAbbreviations

immunology↗

bioRxiv2017

IGoR: A Tool For High-Throughput Immune Repertoire Analysis

High throughput immune repertoire sequencing is promising to lead to new statistical diagnostic tools for medicine and biology. Successful implementations of these methods require a correct characterization, analysis and interpretation of these datasets. We present IGoR - a new comprehensive tool that takes B or T-cell receptors sequence reads and quantitatively characterizes the statistics of receptor generation from both cDNA and gDNA. It probabilistically annotates sequences and its modular structure can investigate models of increasing biological complexity for different organisms. For B-cells IGoR returns the hypermutation statistics, which we use to reveal co-localization of hypermutations along the sequence. We demonstrate that IGoR outperforms existing tools in accuracy and estimate the sample sizes needed for reliable repertoire characterization.

immunology↗

bioRxiv2017

Overexpression Of Hypoxia-Inducible Factor 1 Alpha Improves Immunomodulation By Dental Mesenchymal Stem Cells

BackgroundHuman dental mesenchymal stem cells (MSCs) are considered as highly accessible and attractive MSCs for use in regenerative medicine, yet some of their features are not as well characterized as in other MSCs. Hypoxia-preconditioning and hypoxia inducible factor 1 alpha (HIF-1 alpha) overexpression significantly improve MSC therapeutics, but the mechanisms involved are not fully understood. In the present study, we characterize immunomodulatory properties of dental MSCs and determine changes in their ability to modulate adaptive and innate immune populations after HIF-1 alpha overexpression.\n\nMethodsHuman dental MSCs were stably transduced with GFP (MSCs) or GFP-HIF-1 alpha lentivirus vectors (HIF-MSCs). Hypoxic-like metabolic profile was confirmed by mitochondrial and glycolysis stress test. Capacity of HIF-MSCs to modulate T cell activation, dendritic cell differentiation, monocyte migration and polarizations towards macrophages and NK cell lytic activity was assessed by a number of functional assays in co-cultures. Expression of relevant factors were determined by PCR analysis and ELISA.\n\nResultsWhile HIF-1 alpha overexpression did not modify inhibition of T cell activation by MSCs, HIF-MSCs impaired dendritic cell differentiation more efficiently. HIF-MSCs induced also higher attraction of monocytes, which differentiate into suppressor macrophages, and exhibited enhanced resistance to NK cell-mediated lysis, which support the improved therapeutic capacity of HIF-MSCs. HIF-MSCs also displayed a pro-angiogenic profile characterized by increased expression of CXCL12/SDF1 and CCL5/RANTES and complete loss of CXCL10/IP10 transcription.\n\nConclusionsImmunomodulation and expression of trophic factors by dental MSCs make them perfect candidates for cell therapy. Overexpression of HIF-1 alpha enhances these features and increases their resistance to allogenic NK cell lysis and, hence, their potential in vivo lifespan. Our results further support the use of HIF-1 alpha-expressing dental MSCs for cell therapy in tissue injury and immune disorders.

immunology↗

bioRxiv2017

Dissecting FcγR Regulation Through a Multivalent Binding Model

Many immune receptors transduce activation across the plasma membrane through their clustering. With Fc{gamma} receptors, this clustering is driven by binding to antibodies of differing affinities that are in turn bound to multivalent antigen. As a consequence of this activation mechanism, accounting for and rationally manipulating IgG effector function is complicated by, among other factors, differing affinities between Fc{gamma}R species and changes in the valency of antigen binding. In this study, we show that a model of multivalent receptor-ligand binding can effectively account for the contribution of IgG-Fc{gamma}R affinity and immune complex valency. This model in turn enables us to make specific predictions about the effect of immune complexes of defined composition. In total, these results enable both rational immune complex design for a desired IgG effector function and the deconvolution of effector function by immune complexes.\n\nSummary pointsO_LIAvidity most prominently modulates low-affinity Fc{gamma}R-immune complex binding\nC_LIO_LIA multivalent binding model can quantitatively predict Fc{gamma}R-immune complex binding\nC_LIO_LIImmune complex avidity has an outsized contribution to Fc{gamma}R multimerizationas compared to binding\nC_LIO_LIA binding model deconvoles and predicts the influence of interventions modulating in vivo Fc{gamma}R-driven effector function\nC_LI

immunology↗

bioRxiv2017

The eIF2α Kinase Heme Regulated Inhibitor (HRI) Protects The Host From Infection By Regulating Intracellular Pathogen Trafficking

Phosphorylation of eIF2 by its kinases is a stress response universally conserved among the eukaryota. Previously, we reported that the eIF2 kinases Heme Regulator Inhibitor (HRI) and Protein Kinase R (PKR) control distinct activities of diverse bacterial pathogens. Specifically for Listeria monocytogenes, it was shown that in HRI-deficient cells there was a reduction in the translocation of the pathogen to the cytosolic compartment as well as reduced loading of pathogen-derived antigens on MHC-1 complexes. Here we show that Hri -/- mice, as well as wild-type mice treated with a HRI inhibitor, are more susceptible to listeriosis. In the first few hours of L. monocytogenes infection, Hri -/- mice supported greater pathogen proliferation in the liver compared to that observed in Hri +/+ mice. This greater susceptibility of Hri -/- mice was not due to deficits in immune cell development as proportions and numbers of innate and adaptive cell compartments were largely normal and these mice could mount potent antibody responses to a model T cell-dependent antigen. Using in vitro cellular infection assays, we show that the rate of pathogen efflux from infected Hri -/- macrophages and fibroblasts is significantly higher than that observed in infected Hri +/+ cells. In contrast to the stark differences between Hri +/+ and Hri -/- cells in the infection dynamics of virulent L. monocytogenes, HRI was entirely dispensable for killing non-virulent strains of L. monocytogenes. These results suggest that in wild-type cells, HRI helps ensure the cellular confinement of virulent L. monocytogenes and loading of cytosolic-derived antigens on MHC-1 complexes that limit pathogen spreading and activating innate immune responses, respectively.

immunology↗

bioRxiv2017

Murine Glomerular Transcriptome Links Endothelial Cell-Specific Molecule-1 Deficiency With Susceptibility To Diabetic Nephropathy

Diabetic nephropathy (DN) is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms which govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1), as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

immunology↗

bioRxiv2017

Characterization Of Vif Domains That Mediate Feline Immunodeficiency Virus Antagonism Of APOBEC3-H And APOBEC3-CH Restriction

Feline immunodeficiency virus (FIV) Vif mediates degradation of two anti-lentiviral feline APOBEC3 (fA3) proteins, fA3Z3 and fA3Z2bZ3. HIV-1 Vif targets the restriction factor human APOBEC3G (A3G, hA3Z2g-Z1c) for proteasome degradation to mediate viral evasion. Despite this similarity, FIV and HIV-1 Vif share limited homology. Vif binds hA3Z2g-Z1c through its N-terminal region, while its C-terminal region binds to an E3-ligase complex containing Cullin5 and Elongin B/C. Further, HIV-1 Vif contains critical domains in its C-terminus, including an adjacent BC box, the only shared domain between FIV and HIV-1 Vif, and a non-classical zinc finger (HCCH) domain. Felid lentivirus Vif, however, contains a highly conserved KCCC motif. While both Vifs have evolved to counteract select A3 antiretroviral proteins, the FIV Vif domains necessary to target fA3s for degradation are incompletely understood. To identify these domains, we used the well-characterized HIV-1 Vif domains to show that distinct mutations within the BC box of FIV Vif prevent fA3Z3 and fA3Z2bZ3 degradation and reduce virion infectivity. We also found that mutating any single residue in the KCCC motif blocked fA3 targeting and impaired FIV infectivity and replication. These mutations also failed to disrupt the FIV Vif and Cullin5 interaction. Further, we showed that, in contrast to the HCCH domain in HIV-1 Vif, the KCCC domain of FIV Vif does not bind zinc. However, unlike HIV-1 Vif, FIV Vif (C36 isolate) reduces intracellular levels of co-expressed Cullin5 proteins, a novel finding. Our results reveal important C-terminal residues in FIV Vif and show that the BC box and KCCC regions are critical for fA3 degradation, infectivity, and spreading replication.

immunology↗

bioRxiv2017

Beyond Autoantibodies: Biological Roles Of Human Autoreactive B Cells In Rheumatoid Arthritis Revealed By Whole Transcriptome Profiling

Although the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. Here we present the first comprehensive transcriptome profile of human autoreactive B cells in an autoimmune disease by performing RNA-sequencing of citrulline-specific B cells from RA patients. In order to facilitate a comprehensive understanding of the profile of these citrulline-specific (RA-CCPPOS) B cells, we performed comparative analyses to both citrulline-negative (RA-CCPNEG) B cells from the same donors, and identified 431 differentially expressed genes (DEGs); and hemagglutinin-specific (HA) B cells from healthy individuals and identified 1658 DEGs. Three-way comparisons of these B cell populations demonstrated that RA-CCPPOS B cells, in comparison to the RA-CCPNEG B cells, demonstrate a potential role in protein citrullination and inflammation; RA-CCPPOS B cells in comparison to HA-specific B cells demonstrate RA-specific signatures like the expression of pro-inflammatory cytokines, chemokines, costimulatory molecules and B-cell activation cascades; and all B cells from RA patients demonstrated a significant impact of the multitude of TNF signaling pathways. Furthermore, transcription factor profiling suggested that cyclic AMP (cAMP) related pathways and downstream signaling molecules are selectively enriched in RA-CCPPOS cells in comparison to the other two B cell subsets. We advanced the understanding of the citrulline reactive B cells in RA pathophysiology by documenting and validating two novel observations in independent cohorts of patients: (1) the expression of IL15R is restricted to citrulline-specific cells within RA patients and the concentration of soluble IL15R is elevated in the sera of RA patients, (2) B cells from RA patients are capable of producing epidermal growth factor ligand, amphiregulin (AREG) which in turn has a direct impact on the mechanistic effectors of RA, osteoclasts and fibroblastlike synoviocytes (FLS). Overall, our comprehensive dataset identifies several existing FDA-approved drugs that can potentially be repurposed for RA and can serve as a foundation for studying the multi-faceted roles of B cells in other autoimmune diseases.

immunology↗

bioRxiv2017

Signatures of Selection in the Human Antibody Repertoire: Selective Sweeps, Competing Subclones, and Neutral Drift

Antibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the molecular signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses of five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the linkage between B cell fitness and antibody binding affinity, we demonstrated the potential for using signatures of selection to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.\n\nOne Sentence SummaryMolecular signatures of somatic evolution reveal that diverse evolutionary processes ranging from strong positive selection to neutral drift sculpt human antibodies.

immunology↗

bioRxiv2017

Mycophenolate Mofetil Increases Inflammation Resolution In Zebrafish Via Neutrophil Apoptosis

Mycophenolate mofetil (MMF) is an immunosuppressive agent used in the treatment of autoimmune and inflammatory conditions, and following organ transplant. MMF treatment results in lymphopenia via the depletion of purines required for DNA synthesis. While the primary effect of MMF treatment is thought to be via the depletion of lymphocytes, MMF has also been associated with innate immune defects, including neutropenia and neutrophil dysplasia. Here, we address the question of MMF specific effects on neutrophils in an in vivo model of neutrophil inflammation in zebrafish. We find that, following tissue injury, MMF increases resolution of neutrophilic inflammation via increased neutrophil apoptosis. Critically, we identify that the effect of MMF is distinct from DNA synthesis inhibition by using the competitive inhibitor of purine nucleotide incorporation, azathioprine. Therefore, we propose that increased neutrophil cell death during inflammatory insult may play a role in neutrophil defects associated with MMF treatment.

immunology↗

bioRxiv2017

Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV acquisition and cell-associated virus loads in infant rhesus monkeys.

Vertical HIV-1 transmission via breastfeeding is the predominant contributor to pediatric infections that are ongoing in this era of highly effective antiretroviral therapy (ART). Remarkably, only ~10% of infants chronically exposed to the virus via breastfeeding from untreated HIV-infected mothers become infected, suggesting the presence of naturally protective factors in breast milk. HIV-specific maternal antibodies are obvious candidates as potential contributors to this protection. This study assessed the protective capacity of common HIV envelope-specific non-broadly neutralizing antibodies isolated from breast milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral challenge model. Prior to oral SHIV challenge, infant RMs were i.v. infused with either a single weakly-neutralizing monoclonal antibody (mAb), a tri-mAb cocktail with neutralizing and ADCC functionalities, or an anti-influenza HA control mAb. Of these groups, the fewest tri-mAb-treated infants developed plasma viremia (2/6, 3/6, and 6/8 animals viremic in tri-mAb, single-mAb, and control mAb groups, respectively). Tri-mAb-treated infants demonstrated significantly fewer transmitted/founder SHIV variants in plasma and decreased peripheral CD4+ T cell proviral loads at 8 week post-challenge compared to control mAb-treated infants. Abortive infection was observed as detectable CD4+ T cell provirus in non-viremic control mAb- and single-mAb-, but not tri-mAb-treated animals. Taken together, these results support the potential viability of maternal or infant vaccine strategies that elicit non-broadly neutralizing antibodies to prevent vertical transmission of HIV through breastfeeding.

immunology↗