A5075089406- Mosquito-borne diseases and control
- Viral Infections and Vectors
- Malaria Research and Control
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Virology and Viral Diseases
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Insect symbiosis and bacterial influences
- Invertebrate Immune Response Mechanisms
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- Computational Drug Discovery Methods
- interferon and immune responses
- Speech Recognition and Synthesis
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Viral gastroenteritis research and epidemiology
- Language Development and Disorders
- Transgenic Plants and Applications
- Clinical practice guidelines implementation
- Dengue and Mosquito Control Research
- Bacteriophages and microbial interactions
- Surgical site infection prevention
- Maternal and fetal healthcare
Itasca Consultants (United States)
2020-2021
Fred Hutch Cancer Center
2014-2019
University of California, Berkeley
2010-2017
Washington University in St. Louis
2013
Berkeley College
2011
University Medical Center New Orleans
1995
Louisiana State University
1995
Massachusetts Institute of Technology
1977
Immunity to one of the four dengue virus (DV) serotypes can increase disease severity in humans upon subsequent infection with another DV serotype. Serotype cross-reactive antibodies facilitate myeloid cells vitro by promoting entry via Fcgamma receptors (FcgammaR), a process known as antibody-dependent enhancement (ADE). However, despite decades investigation, no vivo model for antibody has been described. Analogous human infants who receive anti-DV transplacental transfer and develop...
Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Fever severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants inapparent versus symptomatic infection outcome. Here, we analyzed over 2,000 2004 2011 in prospective pediatric cohort study Managua, Nicaragua. Symptomatic...
Abstract Over 75% of malaria-attributable deaths occur in children under the age 5 years. However, first malaria vaccine recommended by World Health Organization (WHO) for pediatric use, RTS,S/AS01 (Mosquirix), has modest efficacy. Complementary strategies, including monoclonal antibodies, will be important efforts to eradicate malaria. Here we characterize circulating B cell repertoires 45 vaccinees and discover antibodies development as potential therapeutics. We generated >28,000...
ABSTRACT Dengue virus (DENV) is the most prevalent insect-transmitted viral disease in humans globally, and currently no specific therapy or vaccine available. Protection against DENV other related flaviviruses associated with development of antibodies envelope (E) protein. Although prior studies have characterized neutralizing activity monoclonal (MAbs) type 2 (DENV-2), none compared simultaneously inhibitory a genetically diverse range strains vitro , protective capacity animals,...
Dengue viruses (DENV) are mosquito-borne flaviviruses of global importance. DENV exist as four serotypes, DENV1-DENV4. Following a primary infection, individuals produce DENV-specific antibodies that bind only to the serotype infection and other cross-react with two or more serotypes. People exposed secondary another at greater risk developing severe forms dengue disease. The increased in people experiencing repeat infections appear be due, least part, ability pre-existing cross-reactive...
Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes virus (DENV). At present, no vaccine or antiviral therapies available against dengue. Here, we characterized a panel eight human mouse-human chimeric monoclonal antibodies (MAbs) their modified variants lacking effector function dissected mechanism by which some protect antibody-enhanced lethal DENV infection. We found that neutralizing MAbs...
Abstract The most advanced P. falciparum circumsporozoite protein-based malaria vaccine, RTS,S/AS01 (RTS,S), confers partial protection but with antibody titers that wane relatively rapidly, highlighting the need to elicit more potent and durable responses. Here, we elucidate crystal structures, binding affinities kinetics, in vivo of eight anti-NANP antibodies derived from an RTS,S phase 2a trial encoded by three different heavy-chain germline genes. structures reinforce importance...
The lack of reliable, high-throughput tools for characterizing anti-dengue virus (DENV) antibodies in large numbers serum samples has been an obstacle understanding the impact neutralizing on disease progression and vaccine efficacy. A reporter system using pseudoinfectious DENV particles (RVPs) was previously developed by others to facilitate genetic manipulation biological characterization virions. In current study, we demonstrate diagnostic utility RVPs measuring human against all four...
A small animal model for studying dengue disease is of critical importance to furthering many areas research, including host immunity, pathogenesis, and drug vaccine development. Recent characterization the AG129 mouse has demonstrated it be one only models at this time that permits infection by all four serotypes virus (DENV), supports replication in relevant cell tissue types comparable human infection, allows antibody-mediated protection enhancement DENV infection. Thus, enables testing...
Dengue virus (DENV) is the leading cause of arboviral diseases in humans worldwide. The envelope (E) protein DENV major target neutralizing antibodies (Abs). Previous studies have shown that a significant proportion anti-E Abs human serum after infection recognize highly conserved fusion loop (FL) E protein. role anti-FL protection against subsequent versus pathogenesis remains unclear. A monoclonal Ab was used as standard virion-capture ELISA to measure concentration Abs, [anti-E Abs],...
Antibodies that mediate killing of HIV-infected cells through antibody-dependent cellular cytotoxicity (ADCC) have been implicated in protection from HIV infection and disease progression. Despite these observations, types antibodies are understudied compared to neutralizing antibodies. Here we describe four monoclonal (mAbs) obtained one individual target the transmembrane protein, gp41, ADCC activity. These mAbs arose independent B cell lineages suggesting this individual, multiple...
Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe disease manifestations that can occur following sequential infection with different virus serotypes (DENV1-4). At present, there no licensed therapies to treat DENV-induced disease. DHF DSS thought be mediated by serotype cross-reactive antibodies facilitate antibody-dependent enhancement (ADE) binding viral antigens then Fcγ receptors (FcγR) on target myeloid cells. Using genetically engineered DENV-specific...
Highlights•Neutralizing antibodies develop upon initial HIV infection and superinfection•Polyclonal antibody response required to describe plasma breadth potency•QA013.2 arises in the superinfecting virus targets N332•Viral escape involves N332 mutation reemergence of initial, resistant virusSummaryEliciting broad potent HIV-specific neutralizing responses represents holy grail vaccine efforts. Data from singly infected individuals with activity targeting one epitope have guided our...
ABSTRACT Dengue viruses are the most common arthropod-transmitted viral infection, with an estimated 390 million human infections annually and ∼3.6 billion people at risk. Currently, there no approved vaccines or therapeutics available to control global dengue virus disease burden. In this study, we demonstrate binding, neutralizing activity, therapeutic capacity of a novel bispecific d ual- ffinity r e t argeting molecule (DART) that limits infection all four serotypes virus.
Dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS) are life-threatening complications following infection with one of the four serotypes virus (DENV).At present, no vaccine or antiviral therapies available against dengue.Here, we characterized a panel eight human mouse-human chimeric monoclonal antibodies (MAbs) their modified variants lacking effector function dissected mechanism by which some protect antibodyenhanced lethal DENV infection.We found that neutralizing MAbs recognize...
Prime-boost vaccination with S. Typhi Vi capsule induces convergent antibodies whose function depends on specificity and avidity.
Abstract Over 80% of malaria-attributable deaths are in children under five. However, the only malaria vaccine recommended by World Health Organization (WHO) for paediatric use, Mosquirix™, has limited efficacy. Complementary strategies, like monoclonal antibodies (mAbs), will be required to eradicate malaria. To discover new anti-malaria mAbs, we evaluated >28,000 antibody sequences from circulating B cells obtained 45 Mosquirix™ vaccinees and selected 369 testing. Many bound...
Endomyometritis following parturition is a major cause of maternal morbidity. It most common cesarean delivery, especially in certain high-risk patient populations. The infection usually caused by bacteria the cervicovaginal tract that are inoculated into uterus during labor and delivery. Both anaerobes aerobes thought to be involved disease process. A prompt diagnosis based on clinical suspicion, thorough physical examination, adjunctive laboratory measures necessary insure effective...
A number of studies have shown that infants as young one month age are able to detect changes in place articulation among the voiced stop consonants English [Moffitt, 1971; Morse, 1972; Eimas, 1974]. In each these studies, stimuli were three-formant synthetic patterns which desired realized by manipulating starting frequencies F2 and F3 transitions. The present experiment was designed examine infant's ability use additional acoustic information provided consonantal release burst making /d-g/...