Biology subjects

Duque, D.

Publications and source records attributed to Duque, D..

9 recordsLinked to original sources

bioRxiv2025

Durability of DNA-LNP and mRNA-LNP Vaccine-Induced Immunity Against SARS-CoV-2 XBB.1.5

mRNA-lipid nanoparticle (LNP) vaccines induce robust adaptive immune responses and have proven highly effective against SARS-CoV-2. However, their long-term effectiveness is limited by waning humoral responses, which decline substantially within the first six months post-boost vaccination. DNA-LNPs are being investigated as an alternative vaccine platform, offering prolonged antigen expression and robust immunity. Here, we present the first comparison of SARS-CoV-2 DNA- and mRNA-LNP vaccines in a long-term in vivo challenge model. Both nucleic acid platforms induced strong neutralizing antibody responses and conferred equivalent protection in Syrian hamsters challenged three weeks post-boost. Notably, DNA-LNP vaccination maintained high binding and neutralizing antibody titers six months post-boost, whereas mRNA-LNPs exhibited a marked decline. Correspondingly, while DNA-LNPs completely protected from weight loss, viral replication, and lung pathology at this late timepoint, mRNA-LNP vaccination conferred minimal protection. These findings demonstrate that DNA-LNPs can sustain durable immunity, highlighting their potential as a next-generation vaccine platform that could reduce the need for frequent boosters.

immunology↗

bioRxiv2024

Temporal Coherence Shapes Cortical Responses to Speech Mixtures in a Ferret Cocktail Party

Segregation of complex sounds such as speech, music and animal vocalizations as they simultaneously emanate from multiple sources (referred to as the "cocktail party problem") is a remarkable ability that is common in humans and animals alike. The neural underpinnings of this process have been extensively studied behaviorally and physiologically in non-human animals primarily with simplified sounds (tones and noise sequences). In humans, segregation experiments utilizing more complex speech mixtures are common; but physiological experiments have relied on EEG/MEG/ECoG recordings that sample activity from thousands of neurons, often obscuring the detailed processes that give rise to the observed segregation. The present study combines the insights from animal single-unit physiology with segregation of speech-like mixtures. Ferrets were trained to attend to a female voice and detect a target word, both in presence or absence of a concurrent, equally salient male voice. Single neuron recordings were obtained from primary and secondary ferret auditory cortical fields, as well as frontal cortex. During task performance, representation of the female words became more enhanced relative to those of the (distractor) male in all cortical regions, especially in the higher auditory cortical field. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings are consistent with the temporal coherence theory whereby attention to a target voice anchors neural activity in cortical networks hence binding together channels that are coherently temporally-modulated with the target, and ultimately forming a common auditory stream.

neuroscience↗

bioRxiv2022

Integrated Immunopeptidomics and Proteomics Study Reveals Imbalanced Innate and Adaptive Immune Responses to SARS-Cov-2 Infection

We present an integrated immunopeptidomics and proteomics study of SARS-Cov-2 infection to comprehensively decipher the changes in host cells in response to viral infection. Our results indicated that innate immune response in Calu-3 cells was initiated by TLR3, followed by activation of interferon signaling pathway. Host cells also present viral antigens to the cell surface through both Class I and Class II MHC system for recognition by adaptive immune system. SARS-Cov-2 infection led to the disruption of antigen presentation as demonstrated by higher level of HLA proteins from the flow-through of MHC immunoprecipitation. Glycosylation analysis of HLA proteins from the elution and flow-through of immunoprecipitation revealed that the synthesis and degradation of HLA protein was affected by SARS-Cov-2 infection. This study provided many useful information to study the host response to SARS-Cov-2 infection and would be helpful for the development of therapeutics and vaccine for Covid-19 and future pandemic.

immunology↗

bioRxiv2022

Intranasal Immunization with a Proteosome-Adjuvanted SARS-CoV2 Spike Protein-Based Vaccine is Immunogenic and Efficacious in Mice & Hamsters

With the persistence of the SARS-CoV-2 pandemic and the emergence of novel variants, the development of novel vaccine formulations with enhanced immunogenicity profiles could help reduce disease burden in the future. Intranasally delivered vaccines offer a new modality to prevent SARS-CoV-2 infections through the induction of protective immune responses at the mucosal surface where viral entry occurs. Herein, we evaluated a novel protein subunit vaccine formulation containing a resistin-trimerized prefusion Spike antigen (SmT1v3) and a proteosome-based mucosal adjuvant (BDX301) formulated to enable intranasal immunization. In mice, the formulation induced robust antigen-specific IgG and IgA titers, in the blood and lungs, respectively. In addition, the formulations were highly efficacious in a hamster challenge model, reducing viral load and body weight loss. In both models, the serum antibodies had strong neutralizing activity, preventing the cellular binding of the viral Spike protein based on the ancestral reference strain, the Beta (B.1.351) and Delta (B.1.617.2) variants of concern. As such, this intranasal vaccine formulation warrants further development as a novel SARS-CoV-2 vaccine.

immunology↗

bioRxiv2022

Isolating perceptual biases caused by trial history during auditory categorization

Just as most experiences have their origin in our perceptions, our perceptions can also be fundamentally shaped by our experiences. However, isolating which events in the recent past can impact perceptual judgments remains a difficult question, partly because post-perceptual processes can also introduce strong history dependencies. Two mechanisms have been hypothesized to specifically modulate perception: 1) the repulsive influence caused by previous stimuli and generally labeled as aftereffects, and 2) the modulation caused by stimulus predictions based on learned temporal regularities of the sensory environment, a key assumption in the predictive coding framework. Here, we ask whether these two mechanisms do indeed bias perception by training rats in an auditory task featuring serial correlations along the sequence of stimuli. We develop a detailed behavioral model that isolates the repulsive aftereffect generated by previous stimuli and shows that this repulsion cannot be explained from an interaction between past and current stimuli, and that it is still present in catch trials lacking the current stimulus. Moreover, the model describes that the bias caused by the animals expectation, as they leverage the predictability of the stimulus sequence, is present in a foraging task without the sensory component but with the same serial correlations in the sequence of rewards. These results indicate that the aftereffect and the prediction biases observed during an auditory task can all be revealed in the absence of a sensory stimulus, putting into question their perceptual nature.

neuroscience↗

bioRxiv2021

Arsenal of Nanobodies for Broad-Spectrum Countermeasures against Current and Future SARS-CoV-2 Variants of Concerns

Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The panel of nanobodies were shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across many VoCs; wide-ranging epitopic and mechanistic diversity; high and broad in vitro neutralization potencies; and high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to tackle current and future SARS-CoV-2 variants and SARS-related viruses. Furthermore, the high aerosol-ability of nanobodies provides the option for effective needle-free delivery through inhalation.

bioengineering↗

bioRxiv2021

Pre-training RNNs on ecologically relevant tasks explains sub-optimal behavioral reset

The strategies found by animals facing a new task are determined both by individual experience and by structural priors evolved to leverage the statistics of natural environments. Rats can quickly learn to capitalize on the trial sequence correlations of two-alternative forced choice (2AFC) tasks after correct trials, but consistently deviate from optimal behavior after error trials, when they waive the accumulated evidence. To understand this outcome-dependent gating, we first show that Recurrent Neural Networks (RNNs) trained in the same 2AFC task outperform rats as they can readily learn to use across-trial information both after correct and error trials. We hypothesize that, while RNNs can optimize their behavior in the 2AFC task without any a priori restrictions, rats strategy is constrained by a structural prior adapted to a natural environment in which rewarded and non-rewarded actions provide largely asymmetric information. When pre-training RNNs in a more ecological task with more than two possible choices, networks develop a strategy by which they gate off the across-trial evidence after errors, mimicking rats behavior. Population analyses show that the pre-trained networks form an accurate representation of the sequence statistics independently of the outcome in the previous trial. After error trials, gating is implemented by a change in the network dynamics which temporarily decouples the categorization of the stimulus from the across-trial accumulated evidence. Our results suggest that the suboptimal behavior observed in rats reflects the influence of a structural prior that reacts to errors by isolating the network decision dynamics from the context, ultimately constraining the performance in a 2AFC laboratory task.

neuroscience↗

bioRxiv2021

An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits potent immunity after a single dose.

Development of efficacious single dose vaccines would substantially aid efforts to stop the uncontrolled spread of the COVID-19 pandemic. We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the SARS-CoV-2 spike protein and several adjuvants in an effort to identify a COVID-19 vaccine candidate efficacious after a single dose. The eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced the highest antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, VBI-2902a (prefusion S eVLPs formulated with aluminum phosphate), protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a potential single dose vaccine against COVID-19. HighlightsO_LIVBI-2902a is a VLP-based vaccine candidate against SARS-COV-2 C_LIO_LIVBI-2902a contains VLPs pseudotyped with a modified prefusion SARS-COV-2 S in Alum. C_LIO_LIVBI-2902a induces robust neutralization antibody response against SARS-COV-2 S C_LIO_LIVBI-2902a protects hamsters from SARS-CoV-2 induced lung inflammation C_LIO_LIA single dose of VBI-2902a provides protective benefit in hamsters C_LI

immunology↗

bioRxiv2020

More than a feeling: central amygdala mediates social transfer of information about proximity of danger

To survive, an animal must adequately respond to challenges presented by the environment. Social animals can learn about danger from fear of conspecifics which allows them to avoid predation and other threats without costly, first-hand experience. However, it remains unclear as to whether animals can transmit specific information that helps an individual avoid harm or whether the transmitted social signals simply increase vigilance in a non-specific manner. Here we demonstrate that animals can select appropriate defensive strategies in a novel environment depending on cues from the conspecific and, using opsins targeted to behaviorally activated neurons, identify distinct neuronal circuits in the central amygdala (CeA) that are crucial for choosing a context-appropriate reaction. The identified circuits differ in molecular markers and patterns of connectivity. Thus, we show that social signals carry explicit information about proximity of danger, necessary for choosing a context-appropriate reaction, and that the choosing process is mediated by the CeA circuits.

neuroscience↗