A5102000244- Respiratory viral infections research
- Viral Infections and Vectors
- Virology and Viral Diseases
- Mosquito-borne diseases and control
- Malaria Research and Control
- Influenza Virus Research Studies
- Neonatal and fetal brain pathology
- Viral gastroenteritis research and epidemiology
- Neonatal Respiratory Health Research
- Neuroscience of respiration and sleep
- Pneumonia and Respiratory Infections
- Vibrio bacteria research studies
- Child and Adolescent Psychosocial and Emotional Development
- Tuberculosis Research and Epidemiology
- Asthma and respiratory diseases
- Vaccine Coverage and Hesitancy
- Gut microbiota and health
- School Health and Nursing Education
- Tracheal and airway disorders
- interferon and immune responses
- Microbial infections and disease research
- Birth, Development, and Health
- Congenital Heart Disease Studies
- HIV Research and Treatment
- Viral Infections and Outbreaks Research
University of Michigan
2019-2024
National Institutes of Health
2001-2023
National Institute of Allergy and Infectious Diseases
2000-2023
Gates Foundation
2022-2023
GlaxoSmithKline (United States)
2018-2022
Gates (United States)
2022
Jena University Hospital
2014-2021
Universities at Shady Grove
2021
Friedrich Schiller University Jena
2014-2019
GlaxoSmithKline (Belgium)
2017
Vaccine efficacy (VE) estimates are crucial for assessing the suitability of dengue vaccine candidates public health implementation, but trials subject to a known bias estimate VE toward null if heterogeneous exposure is not accounted in analysis trial data. In light many well-characterized sources heterogeneity virus (DENV) transmission, our goal was potential magnitude this hypothetical vaccine. To ensure that we realistically modeled exposure, simulated city-wide DENV transmission and...
We have recently shown that non-viral gene therapy can stabilise the decline of lung function in patients with cystic fibrosis (CF). However, effect was modest, and more potent transfer agents are still required. Fuson protein (F)/Hemagglutinin/Neuraminidase (HN)-pseudotyped lentiviral vectors efficient for than preclinical models. In preparation a first-in-man CF trial using vector, we undertaken key translational studies. Regulatory-compliant carrying range promoter/enhancer elements were...
ABSTRACT Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express major protective antigens of respiratory syncytial (RSV) order create bivalent mucosal vaccine against RSV HPIV3. The attenuation rB/HPIV3 is provided by host range restriction BPIV3 backbone primates. G open reading frames (ORFs) placed under control transcription signals inserted individually...
Severe dengue has been attributed to antibody-dependent enhancement during a second infection with virus. A recent study provides evidence for, and an elaboration of, this mechanism.
The safety and immunogenicity of four formulations an investigational tetravalent dengue purified inactivated vaccine (DPIV), formulated at 1 or 4 μg with aluminum hydroxide (alum) adjuvant system (AS01 E AS03 B ), were evaluated in a first-time-in-human, placebo-controlled, randomized, observer-blind, phase trial the continental United States. Two doses placebo administered intramuscularly weeks apart to 100 healthy adults 18–39 years age, randomized 1:1:1:1:1 receive one DPIV saline...
This study examines the contribution of fusion (F) and hemagglutinin-neuraminidase (HN) glycoprotein genes bovine parainfluenza virus type 3 (BPIV3) to its restricted replication in respiratory tract nonhuman primates. A chimeric recombinant human (HPIV3) containing BPIV3 F HN place own reciprocal consisting bearing HPIV3 (rBPIV3-F(H)HN(H)) were generated assess effect substitution on upper lower rhesus monkeys. The viruses readily recovered replicated simian LLC-MK2 cells a level comparable...
ABSTRACT Reverse genetics was used to develop a two-component, trivalent live attenuated vaccine against human parainfluenza virus type 3 (HPIV3) and respiratory syncytial (RSV) subgroups A B. The backbone for each of the two components this recombinant bovine/human PIV3 (rB/HPIV3), BPIV3 in which bovine HN F protective antigens are replaced by their HPIV3 counterparts (48). This chimera retains well-characterized host range attenuation phenotype BPIV3, appears be appropriate immunization...
Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns.
The safety and immunogenicity of four adjuvanted formulations an investigational tetravalent dengue purified inactivated vaccine (DPIV) were evaluated in a predominantly dengue-primed population Puerto Rico. In this placebo-controlled, randomized, observer-blind, phase I trial, 100 healthy adults randomized 1:1:1:1:1 to receive DPIV at Day (D)0 D28 (1 μg per virus [DENV] type 1–4 with either alum, AS01 E or AS03 B , 4 DENV alum) saline placebo. Functional antibody responses assessed using...
The rDEN4Delta30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4Delta30 parent virus. In present study, 28 healthy adult volunteers were randomized receive either 10(5) plaque-forming unit (PFU) of (20) or placebo (8) as single subcutaneous injection. Volunteers evaluated for safety every other day 16 days. Serum neutralizing antibody titer against DEN4 was determined at study 28, 42, and 180. infected all vaccinees well tolerated...
Dengue is an emerging infectious disease that has become the most important arboviral infection worldwide. There are four serotypes of dengue virus, DENV-1, DENV-2, DENV-3, and DENV-4, each capable causing full spectrum disease. rDEN1Δ30 a live attenuated investigational vaccine for prevention DENV-1 illness also component tetravalent DENV currently in Phase I evaluation. A single subcutaneous dose was previously shown to be safe immunogenic healthy adults. In current randomized...
Dengue is a major public health problem worldwide. Although several drug candidates have been evaluated in randomized controlled trials, none has effective and at present, early recognition of severe dengue timely supportive care are used to reduce mortality. While the first vaccine was recently licensed, other late stage clinical future decisions regarding widespread deployment vaccines and/or therapeutics will require evidence product safety, efficacy effectiveness. Standard, quantifiable...
Immunization strategies against tuberculosis (TB) that confer better protection than neonatal vaccination with the 101-year-old Bacille Calmette-Guerin (BCG) are urgently needed to control epidemic, but clinical development is hampered by a lack of established immune correlates (CoPs). Two phase 2b trials offer first opportunity discover human CoPs TB. Adolescent BCG re-vaccination showed partial Mycobacterium (Mtb) infection, as measured sustained IFNγ release assay (IGRA) conversion. Adult...
Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C-), a in which expression of the C proteins (C', C, Y1, and Y2) silenced without affecting amino acid sequence P protein. Infectious rHPIV1-P(C-) readily recovered from cDNA, indicating that four were not essential for replication. Early during infection vitro, replicated as efficiently wild-type (wt) HPIV1, but its titer subsequently decreased coincident with onset an extensive cytopathic effect observed...
rDEN4Delta30-4995 is a live attenuated dengue virus type 4 (DENV4) vaccine candidate specifically designed as further derivative of the rDEN4Delta30 parent virus. In previous study, 5 20 vaccinees who received 10(5) plaque-forming units (PFU) developed transient elevation serum alanine aminotransferase (ALT) level and an asymptomatic maculopapular rash in 10 20. current 28 healthy adult volunteers were randomized to receive PFU (20) or placebo (8) single subcutaneous injection. The was safe,...
Background. Human metapneumovirus (HMPV) causes lower respiratory tract infections in young children. rHMPV-SHs is a recombinant HMPV (rHMPV) based on biologically derived wild-type strain. We characterized its infectivity and immunogenicity healthy adults to determine whether it would be suitable for use as the parent virus development of live attenuated rHMPV vaccines.
Disturbances of fetal autonomic brain development can be evaluated from heart rate patterns reflecting the activity nervous system. Although pattern analysis cardiotocographic (CTG) recordings is established for surveillance, temporal resolution low. Fetal magnetocardiography (MCG), however, provides stable continuous at a higher combined with more precise variability (HRV) analysis. A direct comparison CTG and MCG based HRV pending. The aims present study are (i) to compare maturation age...