Phase 1 clinical trial of Hantaan and Puumala virus DNA vaccines delivered by needle-free injection.

Hantaan virus (HTNV) and Puumala virus (PUUV) are pathogenic zoonoses found in Asia and Europe, respectively. We conducted a randomized Phase 1 clinical trial of individual HTNV and PUUV DNA vaccines targeting the envelope glycoproteins (GnGc), as well as a combined HTNV/PUUV DNA vaccine delivered at varying doses using the PharmaJet Stratis® needle-free injection system (NCT02776761). Cohort 1 and 2 vaccines consisted of 2 mg/vaccination of HTNV or PUUV plasmid, respectively.

Safety and immunogenicity of a next-generation live-attenuated yellow fever vaccine produced in a Vero cell line in the USA: a phase 1 randomised, observer-blind, active-controlled, dose-ranging clinical trial.

Background: Recent outbreaks between 2015-17 and production delays have led to a yellow fever vaccine shortage. Therefore, there is an urgent need for new yellow fever vaccines with improved production scalability. A next-generation live-attenuated yellow fever vaccine candidate (vYF), produced in a Vero cell line has shown similar immunogenicity to licensed yellow fever vaccines in preclinical studies.

Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Trial.

The safety and immunogenicity of the two-dose Ebola vaccine regimen MVA-BN-Filo, Ad26.ZEBOV, 14 days apart, was evaluated in people without HIV (PWOH) and living with HIV (PLWH). In this observer-blind, placebo-controlled, phase 2 trial, healthy adults were randomized (4:1) to receive MVA-BN-Filo (dose 1) and Ad26.

SARS-CoV-2 recombinant spike ferritin nanoparticle vaccine adjuvanted with Army Liposome Formulation containing monophosphoryl lipid A and QS-21: a phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial.

Background: A self-assembling SARS-CoV-2 WA-1 recombinant spike ferritin nanoparticle (SpFN) vaccine co-formulated with Army Liposomal Formulation (ALFQ) adjuvant containing monophosphoryl lipid A and QS-21 (SpFN/ALFQ) has shown protective efficacy in animal challenge models. This trial aims to assess the safety and immunogenicity of SpFN/ALFQ in a first-in-human clinical trial.

Methods: In this phase 1, randomised, double-blind, placebo-controlled, first-in-human clinical trial, adults were randomly assigned (5:5:2) to receive 25 μg or 50 μg of SpFN/ALFQ or saline placebo intramuscularly at day 1 and day 29, with an optional open-label third vaccination at day 181.

The Walter Reed Project, Kisumu Field Station: Impact of Research on Malaria Policy, Management, and Prevention.

The Walter Reed Project is a collaboration between the Walter Reed Army Institute of Research of the United States Department of Defense and the Kenya Medical Research Institute. The Kisumu field station, comprising four campuses, has until recently been devoted primarily to research on malaria countermeasures. The Kombewa Clinical Research Center is dedicated to conducting regulated clinical trials of therapeutic and vaccine candidates in development.

The CINAMR (Clinical Information Network-Antimicrobial Resistance) Project: A pilot microbial surveillance using hospitals linked to regional laboratories in Kenya: Study Protocol.

Antimicrobial resistance (AMR) is a global threat and is thought to be acute in low-and middle-income country (LMIC) settings, including in Kenya, but there is limited unbiased surveillance that can provide reliable estimates of its burden. Current efforts to build capacity for microbiology testing in Kenya are unlikely to result in systematic routine microbiological testing in the near term. Therefore, there is little prospect for microbiological support to inform clinical diagnoses nor for indicating the burden of AMR and for guiding empirical choice of antibiotics.

Preferences of Patients and Providers in High-Burden Malaria Settings for Long-Acting Malaria Chemoprevention.

Antimalarial medications are recommended for chemoprevention as part of malaria control programs to decrease the morbidity and mortality related to more than 200 million infections each year. We sought to evaluate patient and provider acceptability of malaria chemoprevention in a long-acting formulation. We administered questionnaires to patients and providers in malaria endemic districts in Kenya and Zambia.

Safety and immunogenicity of a purified inactivated Zika virus vaccine candidate in adults primed with a Japanese encephalitis virus or yellow fever virus vaccine in the USA: a phase 1, randomised, double-blind, placebo-controlled clinical trial.

Background: Zika virus infection is a threat to at-risk populations, causing major birth defects and serious neurological complications. Development of a safe and efficacious Zika virus vaccine is, therefore, a global health priority. Assessment of heterologous flavivirus vaccination is important given co-circulation of Japanese encephalitis virus and yellow fever virus with Zika virus.

Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

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.

Initiation of anti-retroviral/Trimethoprim-Sulfamethoxazole therapy in a longitudinal cohort of HIV-1 positive individuals in Western Kenya rapidly decreases asymptomatic malarial parasitemia.

Interactions between malaria and HIV-1 have important public health implications. Our previous cross-sectional studies showed significant associations between HIV-1 positivity and malarial parasitemia with an increased risk of gametocytemia. In this follow-up longitudinal study, we evaluated these associations to determine the magnitude of asymptomatic parasitemia over time, and to examine the effects of initiating Antiretroviral Therapy (ART) together with the broad-spectrum antibiotic Trimethoprim Sulfamethoxazole (TS) on asymptomatic parasitemia.

Longitudinal and Cross-sectional Analyses of Asymptomatic HIV-1/Malaria Co-infection in Kisumu County, Kenya.

Individuals infected with HIV-1 experience more frequent and more severe episodes of malaria and are likely to harbor asymptomatic parasitemia, thus potentially making them more efficient reservoirs of malaria. Two studies (cross-sectional and longitudinal) were designed in sequence between 2015-2018 and 2018-2020, respectively, to test the hypothesis that HIV-1 infected individuals have higher prevalence of asymptomatic parasitemia and gametocytemia than the HIV-1 negatives. This article describes the overall design of the two studies, encompassing data for the longitudinal study and additional data to the previously published baseline data for the cross-sectional study.

First-in-human assessment of safety and immunogenicity of low and high doses of Plasmodium falciparum malaria protein 013 (FMP013) administered intramuscularly with ALFQ adjuvant in healthy malaria-naïve adults.

The global burden of malaria remains substantial. Circumsporozoite protein (CSP) has been demonstrated to be an effective target antigen, however, improvements that offer more efficacious and more durable protection are still needed. In support of research and development of next-generation malaria vaccines, Walter Reed Army Institute of Research (WRAIR) has developed a CSP-based antigen (FMP013) and a novel adjuvant ALFQ (Army Liposome Formulation containing QS-21).

A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

Background: A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection.

Serological profiles of pan-coronavirus-specific responses in COVID-19 patients using a multiplexed electro-chemiluminescence-based testing platform.

Serological assessment of SARS-CoV-2 specific responses are an essential tool for determining the prevalence of past SARS-CoV-2 infections in the population especially when testing occurs after symptoms have developed and limited contact tracing is in place. The goal of our study was to test a new 10-plex electro-chemiluminescence-based assay to measure IgM and IgG responses to the spike proteins from multiple human coronaviruses including SARS-CoV-2, assess the epitope specificity of the SARS-CoV-2 antibody response against full-length spike protein, receptor-binding domain and N-terminal domain of the spike protein, and the nucleocapsid protein. We carried out the assay on samples collected from three sample groups: subjects diagnosed with COVID-19 from the U.

Systematic review of Marburg virus vaccine nonhuman primate studies and human clinical trials.

Background: Recent deadly outbreaks of Marburg virus underscore the need for an effective vaccine. A summary of the latest research is needed for this WHO priority pathogen. This systematic review aimed to determine progress towards a vaccine for Marburg virus.

An open label study of the safety and efficacy of a single dose of weekly chloroquine and azithromycin administered for malaria prophylaxis in healthy adults challenged with 7G8 chloroquine-resistant Plasmodium falciparum in a controlled human malaria infection model.

Background: Malaria remains the top infectious disease threat facing the U.S. military in many forward operating environments.

Bacteraemia due to in a patient with chronic kidney disease, refractory hypertension and sarcoidosis.

Introduction: spp. are yellow-pigmented Gram-positive coryneform rods found in various environmental sources, such as soil and water samples. They rarely cause human infection, mostly infecting immunocompromised patients and catheter insertion sites, making them challenging to identify in clinical settings.

Guidelines for the prevention of travel-associated illness in older adults.

International travel to the developing world is becoming more common in elderly patients (defined here as individuals greater than 65 years old). When providing pre-travel counseling, providers must appreciate the changing physiology, comorbidities, immunity and pharmacokinetics associated with the aging process to prepare elderly patients for the stressors of international travel. These guidelines present an evidence-based approach to pre-travel counseling, immunization, and pharmacology concerns unique to elderly patients seeking care in a travel clinic setting.