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Osorio, J. E.

Publications and source records attributed to Osorio, J. E..

7 recordsLinked to original sources

An optimized rabies vaccine vehicle for orotopical administration to wild vampire bats.

Rabies vaccination of vampire bats (Desmodus rotundus) has been proposed as a superior control method to culling but has yet to be implemented. Success of rabies vaccination depends on a topical vehicle that spreads through a bat colony via allogrooming while additionally preserving vaccine immunogenicity. This work describes the in vitro and in vivo optimization of a new orotopical gel for rabies vaccine delivery to vampire bats. Autonomous transferability of our carboxymethyl cellulose (CMC) gel vaccine delivery formulation was tested in a microchipped vampire bat colony in rural Jalisco, Mexico. Intra-colony gel uptake was traced using the fluorescent biomarker rhodamine B. Importantly, application of topical treatment of [~]20% of the bat colony resulted in estimated uptake by over 85% of the colony. The in vitro stability of our raccoon poxviral-vectored rabies vaccine candidate within CMC was measured at time points up to 3 months at 40 {degrees}C, 23 {degrees}C, and 4 {degrees}C. Extended storage at 4 {degrees}C and short exposure at higher temperatures of potential vampire bat environments preserved vaccine titers within CMC. Furthermore, physical properties of our CMC formulation were compared to the previously used glycerin jelly at 40 {degrees}C, 20 {degrees}C, and 0 {degrees}C using rheological tests. These tests indicate that CMC exhibits optimal properties for topical application to bats even at extreme temperatures possible during field vaccination. This study advances our rabies vaccination strategy for vampire bats by providing a topical vehicle suitable for field application that may additionally be employed for other significant bat diseases.

ecology↗

Spatiotemporal dispersion of DENV1 genotype V in western Colombia

Dengue virus (DENV) is a significant public health concern in Colombia, with increased transmission of DENV type 1 (DENV-1) in the departments of Risaralda and Valle del Cauca in the Central-West region of the country following a large outbreak in 2019. However, little is known about the source, genetic diversity, and evolution of circulating viruses. We obtained plasma samples from individuals with acute DENV infection and analyzed DENV-1 genetic diversity, phylodynamics, and phylogeography. We found that most viruses belonged to DENV-1 genotype V, and phylogenetic analysis revealed three distinct clades, each of which was most closely related to viruses from neighboring departments of Colombia sampled over the last 5-10 years. Thus, the 2019 outbreak and subsequent DENV-1 circulation was not due to the introduction of a new lineage but rather reflected local DENV-1V dispersion and evolution. We identified amino acid positions under positive selection in structural proteins and NS1, which may have a role in immune evasion and pathogenesis. Overall, our analysis of DENV1 genotype V diversity, evolution and spread within Colombia highlights the important role of genomic surveillance in understanding virus dynamics during endemic circulation and outbreaks.

evolutionary biology↗

Social effects of rabies infection in male vampire bats (Desmodus rotundus)

Abstract (resumen en espanol, S1)Rabies virus (RABV) transmitted by the common vampire bat (Desmodus rotundus) poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host-pathogen dynamics are influenced by two infection-induced behavioral changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioral changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Here, we take advantage of an experiment designed to test the safety and efficacy of an oral rabies vaccine in captive male vampire bats to quantify for the first time how rabies affects allogrooming and aggressive behaviors in the vampire bat. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioral changes of rabid vampire bats.

animal behavior and cognition↗

T Cell Predominant Response to AAV-Spike Protects hACE2 Mice from SARS-CoV-2 Pneumonia

Prevention of COVID-19 is widely believed to depend on neutralization of SARS-CoV-2 by vaccine-induced humoral immunity1,2, raising concern that emerging escape variants may perpetuate the pandemic3-6. Here we show that a single intramuscular injection of Adeno-Associated Virus-6 (AAV6) or AAV9 encoding a modified, N-terminal domain deleted ({Delta}NTD) spike protein induces robust cellular immunity and provides long-term protection in k18-hACE2 transgenic mice from lethal SARS-CoV-2 challenge, associated weight loss and pneumonia independent of vaccine-induced neutralizing humoral immunity. In both mice and macaques, vaccine-induced cellular immunity results in the clearance of transduced muscle fibers coincident with macrophage and CD8+ cytotoxic T cell infiltration at the site of immunization. Additionally, mice demonstrate a strong Type-1 polarized cellular immunophenotype and equivalent ex vivo T cell reactivity to peptides of wt and alpha (B.1.1.7) variant spike. These studies demonstrate not only that AAV6 and AAV9 can function as effective vaccine platforms, but also that vaccines can provide long-term efficacy primarily through the induction of cellular immunity. The findings may provide an alternative approach to containment of the evolving COVID-19 pandemic and have broader implications for the development of variant-agnostic universal vaccines against a wider range of pathogens.

immunology↗

Dog Savior: Immediate Scent-Detection of SARS-COV-2 by Trained Dogs

Molecular tests for viral diagnostics are essential to confront the COVID-19 pandemic, but their production and distribution cannot satisfy the current high demand. Early identification of infected people and their contacts is the key to being able to isolate them and prevent the dissemination of the pathogen; unfortunately, most countries are unable to do this due to the lack of diagnostic tools. Dogs can identify, with a high rate of precision, unique odors of volatile organic compounds generated during an infection; as a result, dogs can diagnose infectious agents by smelling specimens and, sometimes, the body of an infected individual. We trained six dogs of three different breeds to detect SARS-CoV-2 in respiratory secretions of infected patients and evaluated their performance experimentally, comparing it against the gold standard (rRT-PCR). Here we show that viral detection takes one second per specimen. After scent-interrogating 9,200 samples, our six dogs achieved independently and as a group very high sensitivity, specificity, predictive values, accuracy, and likelihood ratio, with very narrow confidence intervals. The highest metric was the negative predictive value, indicating that with a disease prevalence of 7.6%, 99.9% of the specimens indicated as negative by the dogs did not carry the virus. These findings demonstrate that dogs could be useful to track viral infection in humans, allowing COVID-19 free people to return to work safely.

microbiology↗

Ocular and uteroplacental pathology in macaque congenital Zika virus infection

Congenital Zika virus (ZIKV) infection impacts fetal development and pregnancy outcomes. We infected a pregnant rhesus macaque with a Puerto Rican ZIKV isolate in the first trimester. The pregnancy was complicated by preterm premature rupture of membranes (PPROM) and fetal demise 49 days post infection (gestational day 95). Significant pathology at the maternal-fetal interface included acute chorioamnionitis, placental infarcts, and leukocytoclastic vasculitis of the myometrial radial arteries. ZIKV RNA was disseminated throughout the fetus tissues and maternal immune system at necropsy, as assessed by quantitative RT-PCR for viral RNA. Replicating ZIKV was identified in fetal tissues, maternal lymph node, and maternal spleen by fluorescent in situ hybridization for viral replication intermediates. Fetal ocular pathology included a choroidal coloboma, suspected anterior segment dysgenesis, and a dysplastic retina. This is the first report of ocular pathology and prolonged viral replication in both maternal and fetal tissues following congenital ZIKV infection in rhesus macaques. PPROM followed by fetal demise and severe pathology of the visual system have not been described in macaque congenital infection previously; further nonhuman primate studies are needed to determine if an increased risk for PPROM is associated with congenital Zika virus infection.\n\nAuthor summaryA ZIKV infection during pregnancy is associated with malformations in fetal development including, but not limited to, ocular and brain anomalies, such as microcephaly, and stillbirth. The development of an accurate pregnancy model to study the effects of ZIKV will provide insight into vertical transmission, ZIKV tissue distribution, and fetal injury and malformations. Non-human primates closely resemble human in terms of the reproductive system, immunity, placentation and pregnancy. Our study demonstrates that the rhesus macaque is a compelling model in which to study ZIKV during pregnancy due to similar outcomes between the human and rhesus macaque. These similarities include prolonged viremia, vertical transmission, adverse pregnancy outcomes and fetal pathology, including defects in the visual system.

pathology↗

Highly efficient maternal-fetal Zika virus transmission in pregnant rhesus macaques

Infection with Zika virus (ZIKV) is associated with human congenital fetal anomalies. To model fetal outcomes in nonhuman primates, we administered Asian-lineage ZIKV subcutaneously to four pregnant rhesus macaques. While non-pregnant animals clear viremia within 10-12 days, maternal viremia was prolonged in 3 of 4 pregnancies. Fetal head growth velocity in the last month of gestation determined by ultrasound assessment of head circumference was decreased in comparison with biparietal diameter and femur length within each fetus, both within normal range. ZIKV RNA was detected in tissues from all four fetuses at term cesarean section. In all pregnancies, neutrophilic infiltration was present at the maternal-fetal interface (decidua, placenta, fetal membranes), in various fetal tissues, and in fetal retina, choroid, and optic nerve (first trimester infection only). Consistent vertical transmission in this primate model may provide a platform to assess risk factors and test therapeutic interventions for interruption of fetal infection.

pathology↗