Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-10 (of 10 Records) |
Query Trace: Jenks MH[original query] |
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Delayed low-dose oral administration of 4'-fluorouridine inhibits pathogenic arenaviruses in animal models of lethal disease
Welch SR , Spengler JR , Westover JB , Bailey KW , Davies KA , Aida-Ficken V , Bluemling GR , Boardman KM , Wasson SR , Mao S , Kuiper DL , Hager MW , Saindane MT , Andrews MK , Krueger RE , Sticher ZM , Jung KH , Chatterjee P , Shrivastava-Ranjan P , Lo MK , Coleman-McCray JD , Sorvillo TE , Genzer SC , Scholte FEM , Kelly JA , Jenks MH , McMullan LK , Albariño CG , Montgomery JM , Painter GR , Natchus MG , Kolykhalov AA , Gowen BB , Spiropoulou CF , Flint M . Sci Transl Med 2024 16 (774) eado7034 Development of broad-spectrum antiviral therapies is critical for outbreak and pandemic preparedness against emerging and reemerging viruses. Viruses inducing hemorrhagic fevers cause high morbidity and mortality in humans and are associated with several recent international outbreaks, but approved therapies for treating most of these pathogens are lacking. Here, we show that 4'-fluorouridine (4'-FlU; EIDD-2749), an orally available ribonucleoside analog, has antiviral activity against multiple hemorrhagic fever viruses in cell culture, including Nipah virus, Crimean-Congo hemorrhagic fever virus, orthohantaviruses, and arenaviruses. We performed preclinical in vivo evaluation of oral 4'-FlU against two arenaviruses, Old World Lassa virus (LASV) and New World Junín virus (JUNV), in guinea pig models of lethal disease. 4'-FlU demonstrated both advantageous pharmacokinetic characteristics and high efficacy in both of these lethal disease guinea pig models. Additional experiments supported protection of the infected animals even when 4'-FlU delivery was reduced to a low dose of 0.5 milligram per kilogram. To demonstrate clinical utility, 4'-FlU treatment was evaluated when initiated late in the course of infection (12 or 9 days after infection for LASV and JUNV, respectively). Delayed treatment resulted in rapid resolution of clinical signs, demonstrating an extended window for therapeutic intervention. These data support the use of 4'-FlU as a potent and efficacious treatment against highly pathogenic arenaviruses of public health concern with a virus inhibition profile suggesting broad-spectrum utility as an orally available antiviral drug against a wide variety of viral pathogens. |
Identification of a macrocyclic compound targeting the Lassa virus polymerase
Aida-Ficken V , Kelly JA , Chatterjee P , Jenks MH , McMullan LK , Albariño CG , Montgomery JM , Seley-Radtke KL , Spiropoulou CF , Flint M . Antiviral Res 2024 105923 There are no approved vaccines or therapeutics for Lassa virus (LASV) infections. To identify compounds with anti-LASV activity, we conducted a cell-based screening campaign at biosafety level 4 and tested almost 60,000 compounds for activity against an infectious reporter LASV. Hits from this screen included several structurally related macrocycles. The most potent, Mac128, had a sub-micromolar EC(50) against the reporter virus, inhibited wild-type clade IV LASV, and reduced viral titers by 4 orders of magnitude. Mechanistic studies suggested that Mac128 inhibited viral replication at the level of the polymerase. |
Examination of SARS-CoV-2 serological test results from multiple commercial and laboratory platforms with an in-house serum panel
Lester SN , Stumpf M , Freeman BD , Mills L , Schiffer J , Semenova V , Jia T , Desai R , Browning P , Alston B , Ategbole M , Bolcen S , Chen A , David E , Manitis P , Tatum H , Qin Y , Zellner B , Drobeniuc J , Tejada-Strop A , Chatterjee P , Shrivastava-Ranjan P , Jenks MH , McMullan LK , Flint M , Spiropoulou CF , Niemeyer GP , Werner BJ , Bean CJ , Johnson JA , Hoffmaster AR , Satheshkumar PS , Schuh AJ , Owen SM , Thornburg NJ . Access Microbiol 2024 6 (2) Severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) is a novel human coronavirus that was identified in 2019. SARS-CoV-2 infection results in an acute, severe respiratory disease called coronavirus disease 2019 (COVID-19). The emergence and rapid spread of SARS-CoV-2 has led to a global public health crisis, which continues to affect populations across the globe. Real time reverse transcription polymerase chain reaction (rRT-PCR) is the reference standard test for COVID-19 diagnosis. Serological tests are valuable tools for serosurveillance programs and establishing correlates of protection from disease. This study evaluated the performance of one in-house enzyme linked immunosorbent assay (ELISA) utilizing the pre-fusion stabilized ectodomain of SARS-CoV-2 spike (S), two commercially available chemiluminescence assays Ortho VITROS Immunodiagnostic Products Anti-SARS-CoV-2 Total Reagent Pack and Abbott SARS-CoV-2 IgG assay and one commercially available Surrogate Virus Neutralization Test (sVNT), GenScript USA Inc., cPass SARS-CoV-2 Neutralization Antibody Detection Kit for the detection of SARS-CoV-2 specific antibodies. Using a panel of rRT-PCR confirmed COVID-19 patients' sera and a negative control group as a reference standard, all three immunoassays demonstrated high comparable positivity rates and low discordant rates. All three immunoassays were highly sensitive with estimated sensitivities ranging from 95.4-96.6 %. ROC curve analysis indicated that all three immunoassays had high diagnostic accuracies with area under the curve (AUC) values ranging from 0.9698 to 0.9807. High positive correlation was demonstrated among the conventional microneutralization test (MNT) titers and the sVNT inhibition percent values. Our study indicates that independent evaluations are necessary to optimize the overall utility and the interpretation of the results of serological tests. Overall, we demonstrate that all serological tests evaluated in this study are suitable for the detection of SARS-CoV-2 antibodies. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines.
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Mann BR , Hossain J , Lin X , Lester S , Pusch EA , Jones J , Cui D , Chatterjee P , Jenks MH , Morantz EK , Larson GP , Hatta M , Harcourt JL , Tamin A , Li Y , Tao Y , Zhao K , Lacek K , Burroughs A , Wang W , Wilson M , Wong T , Park SH , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Halpin AL , McMullan LK , Lee JS , Xia H , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan VG , Wentworth DE , Zhou B . Nat Commun 2022 13 (1) 4350 ![]() ![]() The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccine-mediated protection from disease. To ascertain and rank the risk of VOCs and VOIs, we analyze the ability of 14 variants (614G, Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu, and Omicron) to escape from mRNA vaccine-induced antibodies. The variants show differential reductions in neutralization and replication by post-vaccination sera. Although the Omicron variant (BA.1, BA.1.1, and BA.2) shows the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retain moderate neutralizing activity against that variant. Therefore, vaccination remains an effective strategy during the COVID-19 pandemic. |
Evaluation of an OV-16 IgG4 enzyme-linked immunosorbent assay in humans and its application to determine the dynamics of antibody responses in a non-human primate model of Onchocerca volvulus infection
Cama VA , McDonald C , Arcury-Quandt A , Eberhard M , Jenks MH , Smith J , Feleke SM , Abanyie F , Thomson L , Wiegand RE , Cantey PT . Am J Trop Med Hyg 2018 99 (4) 1041-1048 Onchocerciasis is a neglected parasitic disease targeted for elimination. Current World Health Organization guidelines for elimination include monitoring antibody responses to the recombinant Onchocerca volvulus antigen OV-16 in children to demonstrate the absence of transmission. We report the performance characteristics of a modified OV-16 enzyme-linked immunosorbent assay (ELISA) and describe anti-OV-16 responses in serum samples from laboratory-inoculated nonhuman primates (NHPs) in relation to microfilariae (mf) in skin snip biopsies. This OV-16 IgG4 ELISA had sensitivity and specificity of 88.2% and 99.7%, respectively, as determined by receiver operator characteristic analysis using a serum panel of 110 positive and 287 negative samples from people infected with other filariae or other parasitic infections. Anti-OV-16 responses in inoculated NHP (N = 9) were evaluated at quarterly intervals for IgM and the four IgG subclasses. Enzyme-linked immunosorbent assay results showed a well-defined IgG4 reactivity pattern and moderate IgG1 antibody responses. Meanwhile, the reactivity by IgG2, IgG3, or IgM did not show a clear pattern. Temporal evolution of IgG4 reactivity was evaluated through monthly testing, showing that NHPs developed anti-OV-16 IgG4 on average at 15 months postinoculation (range: 10-18 months). The average time to detectable mf was also 15 months (range: 11-25). The OV-16 ELISA used in this study was robust and allowed the detection of IgG4 responses, which were observed only among animals with detectable mf (N = 5), four of which showed declines in antibody responses once mf cleared. These findings also confirmed that the most informative antibody subclass responses to OV-16 are IgG4. |
Equine encephalosis virus in India, 2008
Yadav PD , Albarino CG , Nyayanit DA , Guerrero L , Jenks MH , Sarkale P , Nichol ST , Mourya DT . Emerg Infect Dis 2018 24 (5) 898-901 A virus isolated from a sick horse from India in 2008 was confirmed by next-generation sequencing analysis to be equine encephalosis virus (EEV). EEV in India is concerning because several species of Culicoides midge, which play a major role in EEV natural maintenance and transmission, are present in this country. |
Integration of multiplex bead assays for parasitic diseases into a national, population-based serosurvey of women 15-39 years of age in Cambodia
Priest JW , Jenks MH , Moss DM , Mao B , Buth S , Wannemuehler K , Soeung SC , Lucchi NW , Udhayakumar V , Gregory CJ , Huy R , Muth S , Lammie PJ . PLoS Negl Trop Dis 2016 10 (5) e0004699 Collection of surveillance data is essential for monitoring and evaluation of public health programs. Integrated collection of household-based health data, now routinely carried out in many countries through demographic health surveys and multiple indicator surveys, provides critical measures of progress in health delivery. In contrast, biomarker surveys typically focus on single or related measures of malaria infection, HIV status, vaccination coverage, or immunity status for vaccine-preventable diseases (VPD). Here we describe an integrated biomarker survey based on use of a multiplex bead assay (MBA) to simultaneously measure antibody responses to multiple parasitic diseases of public health importance as part of a VPD serological survey in Cambodia. A nationally-representative cluster-based survey was used to collect serum samples from women of child-bearing age. Samples were tested by MBA for immunoglobulin G antibodies recognizing recombinant antigens from Plasmodium falciparum and P. vivax, Wuchereria bancrofti, Toxoplasma gondii, Taenia solium, and Strongyloides stercoralis. Serologic IgG antibody results were useful both for generating national prevalence estimates for the parasitic diseases of interest and for confirming the highly focal distributions of some of these infections. Integrated surveys offer an opportunity to systematically assess the status of multiple public health programs and measure progress toward Millennium Development Goals. |
Tetanus immunity among women aged 15-39 years in Cambodia: A national population-based serosurvey, 2012
Scobie HM , Mao B , Buth S , Wannemuehler KA , Sorensen C , Kannarath C , Jenks MH , Moss DM , Priest JW , Soeung SC , Deming MS , Lammie PJ , Gregory CJ . Clin Vaccine Immunol 2016 23 (7) 546-54 INTRODUCTION: To monitor progress toward maternal and neonatal tetanus elimination (MNTE) in Cambodia, we conducted a nationwide serosurvey of tetanus immunity in 2012. METHODS: Multi-stage cluster sampling was used to select 2,154 women aged 15-39 years. Tetanus toxoid antibodies in sera were measured by gold-standard double antigen ELISA (DAE) and a novel multiplex bead assay (MBA). Antibody concentrations ≥0.01 IU/ml by DAE, or equivalent for MBA, were considered seroprotective. RESULTS: Estimated tetanus seroprotection was 88% (95% CI: 86%-89%); 64% (95% CI: 61%-67%) of women had antibody levels ≥1.0 IU/ml. Seroprotection was significantly lower (p <0.001) among women aged 15-19 years (63%) and 20-24 years (87%) compared with ≥25 years (96%), nulliparous compared with parous (71% vs. 97%), and living in the west compared with other regions (82% vs. 89%). The MBA showed high sensitivity (99% [95% CI: 98%-99%]) and specificity (92% [95% CI: 88%-95%]) compared with DAE. CONCLUSIONS: Findings were compatible with MNTE in Cambodia (≥80% protection). Tetanus immunity gaps should be addressed through strengthened routine immunization and targeted vaccination campaigns. Incorporating tetanus testing in national serosurveys using MBAs, which can measure immunity to multiple pathogens simultaneously, may be beneficial for monitoring MNTE. |
First report of Dracunculus insignis in two naturally infected cats from the northeastern USA
Lucio-Forster A , Eberhard ML , Cama VA , Jenks MH , Jones C , Sanders SY , Pongratz JP , Bowman DD . J Feline Med Surg 2014 16 (2) 194-7 Dracunculiasis is rarely reported in cats, yet over the last few years we have identified two cats with filarioid-like spirurid infections. Case 1 was a 9-year-old cat with pituitary-dependent hyperadrenocorticism from New York state from which four adult dracunculoid nematodes were isolated from its torso. Based on morphometric characteristics and parasite geographic distribution, the specimens were identified as Dracunculus insignis females; at least one of the females was gravid, suggestive of patent infection. Species identification was confirmed through amplification and sequence analysis of nuclear and mitochondrial loci. Case 2 was a 14-year-old diabetic cat from Massachusetts. Formalin-fixed sections were obtained from a subcutaneous mass excised from the left foreleg. Histopathological examination revealed a large nematode with morphometrical characteristics of Dracunculus, surrounded by lymphocytes and sheets of eosinophils. These two cases appear to be the first published reports of dracunculiasis in domestic cats in the USA, and based on the findings from case 1, D insignis may be the species associated with both infections. |
The Peculiar epidemiology of dracunculiasis in Chad
Eberhard ML , Ruiz-Tiben E , Hopkins DR , Farrell C , Toe F , Weiss A , Withers PC Jr , Jenks MH , Thiele EA , Cotton JA , Hance Z , Holroyd N , Cama VA , Tahir MA , Mounda T . Am J Trop Med Hyg 2013 90 (1) 61-70 Dracunculiasis was rediscovered in Chad in 2010 after an apparent absence of 10 years. In April 2012 active village-based surveillance was initiated to determine where, when, and how transmission of the disease was occurring, and to implement interventions to interrupt it. The current epidemiologic pattern of the disease in Chad is unlike that seen previously in Chad or other endemic countries, i.e., no clustering of cases by village or association with a common water source, the average number of worms per person was small, and a large number of dogs were found to be infected. Molecular sequencing suggests these infections were all caused by Dracunculus medinensis. It appears that the infection in dogs is serving as the major driving force sustaining transmission in Chad, that an aberrant life cycle involving a paratenic host common to people and dogs is occurring, and that the cases in humans are sporadic and incidental. |
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