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Background: Limited epidemiologic studies have been conducted in Jordan describing the HIV epidemic. This study aimed to address this gap to inform HIV prevention and control., Methods: A nationally-representative cross-sectional study was conducted among adults living with HIV in Jordan. Laboratory testing included HIV viral load and next-generation-sequencing-based clinical genotype. Log-binomial regression estimated risk ratios (RRs) and 95% confidence intervals (CIs)., Results: Among 231 (70%) participants, most were male (184/80%), and from Jordan (217/94%). Among 188 treatment-experienced-participants (>6 months), 165 (88%) were virally suppressed. High-level resistance was most frequent against nucleoside reverse transcriptase inhibitor (13/81%), and integrase-strand transfer inhibitor (INSTI) (10/62%) drugs among viremic (≥1000 HIV copies/mL) treatment-experienced participants with drug-resistant mutations (DRMs, n = 16). Common HIV subtypes (n = 43) were B (6/14%), A1 (5/12%), and CRF01_AE (5/12%); additionally, novel recombinant forms were detected. In multivariate analysis, independently higher risk for late diagnosis (n = 49) was observed with diagnosis through blood donation (vs check-up: RR 2.20, 95%CI 1.16-4.17) and earlier time-period of diagnosis (1986-2014 vs 2015-2021: RR 2.87, 95%CI 1.46-5.62)., Conclusions: Late diagnosis and INSTI resistance endanger national HIV prevention and treatment in Jordan-high-level resistance to INSTI suggests therapeutic drug monitoring is needed for treatment efficacy and conservation of treatment options., Competing Interests: Declarations of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Optimization of control measures for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk institutional settings (e.g., prisons, nursing homes, or military bases) depends on how transmission dynamics in the broader community influence outbreak risk locally. We calibrated an individual-based transmission model of a military training camp to the number of RT-PCR positive trainees throughout 2020 and 2021. The predicted number of infected new arrivals closely followed adjusted national incidence and increased early outbreak risk after accounting for vaccination coverage, masking compliance, and virus variants. Outbreak size was strongly correlated with the predicted number of off-base infections among staff during training camp. In addition, off-base infections reduced the impact of arrival screening and masking, while the number of infectious trainees upon arrival reduced the impact of vaccination and staff testing. Our results highlight the importance of outside incidence patterns for modulating risk and the optimal mixture of control measures in institutional settings., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Background: WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults., Methods: We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 10 or 1 × 10 11 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056., Findings: Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 10 pu (n=20) or 1 × 10 11 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 10 10 pu group and 545 [276-1078] in the 1 × 10 11 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×10 10 pu group and 27 [95-156] in the 1 ×10 11 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination., Interpretation: This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions., Funding: National Institutes of Health., Competing Interests: Declaration of interests NJS is listed on patents involving cAd3-vectored vaccines. All other authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Genus Flavivirus, which includes 53 virus species, is the leading cause of arthropod-borne diseases in humans. Diagnosis of these viral diseases is complicated by their overlapping epidemiology and clinical manifestations, and the fact that cross-reactive antibody responses are frequently elicited by individuals in response to infection. We developed a bead-based immunoassay to concomitantly profile the isotype and subclass of antibody responses (five isotypes and four subclasses) in parallel with specificity against multiple antigens. Our panel included 22 envelope (E) and non-structural 1 (NS1) proteins of different flaviviruses (Zika (ZIKV), Dengue (DENV), Yellow Fever (YFV), West Nile (WNV), Japanese Encephalitis (JEV) and Tick-Borne Encephalitis (TBEV)) and the envelope protein of Chikungunya virus (CHIKV). Using 54 samples from 40 individuals with ZIKV infection that had been pre-characterized, we identified 1) stronger ZIKV responses in individuals previously exposed to flavivirus compared to flavivirus-naïve individuals; 2) different antibody isotypes depending on the stage of infection: acute, convalescent and late convalescent; 3) cross-reactive responses; and 4) a potential CHIKV infection. The assay had a broad dynamic range (>5 logs) and has the potential to distinguish antigen-specific responses induced by ZIKV infection from cross-reactive responses. The multidimensional data provided by this high-throughput antibody-profiling platform can advance our understanding of the human immune response to flaviviruses as they expand their global reach., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Immunoglobulin M (IgM) is the first antibody induced after the onset of an adaptive immune response against a pathogen or vaccine. Serological assays play a central role in evaluating these adaptive immunological responses. Such assays are not only crucial for the assessment of vaccine immunogenicity, but also inform on exposure to pathogens and cross-reactivity with other viruses. To date, there is no ELISA-based assay available that measures IgM responses against Zaire Ebola virus (ZEBOV). To address this critical need, our laboratory has developed a novel immunoassay capable of detecting total IgM against ZEBOV glycoprotein in serum samples from individuals exposed to the antigen through infection or vaccination. Here, we describe a sensitive, high-throughput, and inexpensive assay that can be performed in any laboratory. The performance criteria of the newly developed ZEBOV glycoprotein-based IgM ELISA were assessed using antisera collected from human patients immunized with the rVSVΔG-ZEBOV-GP vaccine being tested in a phase 1 clinical trial. This assay demonstrates high specificity and sensitivity and will also be a valuable tool in the mission to find immune correlates of protection for a successful Ebola vaccine., (Published by Elsevier B.V.)

Background: A safe, effective, and rapidly scalable vaccine against Zika virus infection is needed. We developed a purified formalin-inactivated Zika virus vaccine (ZPIV) candidate that showed protection in mice and non-human primates against viraemia after Zika virus challenge. Here we present the preliminary results in human beings., Methods: We did three phase 1, placebo-controlled, double-blind trials of ZPIV with aluminium hydroxide adjuvant. In all three studies, healthy adults were randomly assigned by a computer-generated list to receive 5 μg ZPIV or saline placebo, in a ratio of 4:1 at Walter Reed Army Institute of Research, Silver Spring, MD, USA, or of 5:1 at Saint Louis University, Saint Louis, MO, USA, and Beth Israel Deaconess Medical Center, Boston, MA, USA. Vaccinations were given intramuscularly on days 1 and 29. The primary objective was safety and immunogenicity of the ZPIV candidate. We recorded adverse events and Zika virus envelope microneutralisation titres up to day 57. These trials are registered at ClinicalTrials.gov, numbers NCT02963909, NCT02952833, and NCT02937233., Findings: We enrolled 68 participants between Nov 7, 2016, and Jan 25, 2017. One was excluded and 67 participants received two injections of Zika vaccine (n=55) or placebo (n=12). The vaccine caused only mild to moderate adverse events. The most frequent local effects were pain (n=40 [60%]) or tenderness (n=32 [47%]) at the injection site, and the most frequent systemic reactogenic events were fatigue (29 [43%]), headache (26 [39%]), and malaise (15 [22%]). By day 57, 52 (92%) of vaccine recipients had seroconverted (microneutralisation titre ≥1:10), with peak geometric mean titres seen at day 43 and exceeding protective thresholds seen in animal studies., Interpretation: The ZPIV candidate was well tolerated and elicited robust neutralising antibody titres in healthy adults., Funding: Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Respiratory syncytial virus (RSV) remains a leading global cause of infant mortality and adult morbidity. Infection, which recurs throughout life, elicits only short-lived immunity. The development of a safe and efficacious vaccine has, thus far, been elusive. Recent technological advances, however, have yielded promising RSV vaccine candidates that are based on solving atomic-level structures of surface glycoproteins interacting with neutralizing antibodies. The class I fusion glycoprotein, F, serves as the primary antigenic component of most vaccines, and is the target of the only licensed monoclonal antibody product used to reduce the frequency of severe disease in high-risk neonates. However, success of prior F-based vaccines has been limited by the lack of understanding how the conformational rearrangement between a metastable prefusion F (pre-F) and a stable postfusion F (post-F) affected the epitope content. Neutralizing epitopes reside on both conformations, but those specific to pre-F are far more potent than those previously identified and present on post-F. The solution of the pre-F structure and its subsequent characterization and stabilization illustrates the value of a structure-based approach to vaccine development, and provides hope that a safe and effective RSV vaccine is possible., (Published by Elsevier Ltd.)

Background: Epidemiologic research on intentional burns in the United States has mainly been based on small, geographically restricted populations. The current study presents the descriptive epidemiology of intentional burns using data from a large, geographically diverse population of burn patients., Methods: The National Burn Repository (NBR) was queried for patients with intentional burns and analyzed data pertaining to their demographic and medical characteristics; primarily comparing the prevalence proportions of these variables according to specific injury intent., Results: From a total of 54,219 burn patients, 1601 patients who sustained intentional burns were identified; 49% were self-inflicted, and 51% were assault-related. Compared to all other burn patients, intentional burn patients had a larger mean total body surface area (TBSA) burned (22.0% versus 11.3%, p<0.0001), longer hospital stay (19.8 days versus 12.5 days, p<0.0001), and higher mortality (13.9% versus 2.5%, p<0.0001). Self-inflicted compared to assault-related burns were associated with a larger TBSA burned (27.5% versus 16.8%, p<0.0001) and higher mortality (20.8% versus 7.2%, p<0.0001)., Conclusions: Data from this national cohort of burn patients support findings from smaller studies that patients who suffer intentional burns experience excess morbidity and mortality.