A5039200063- Poxvirus research and outbreaks
- Malaria Research and Control
- Herpesvirus Infections and Treatments
- Bacillus and Francisella bacterial research
- Mosquito-borne diseases and control
- Trypanosoma species research and implications
- HIV Research and Treatment
- Viral Infections and Vectors
- Complement system in diseases
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Invertebrate Immune Response Mechanisms
- Zoonotic diseases and public health
- Research on Leishmaniasis Studies
- Viral Infections and Outbreaks Research
- SARS-CoV-2 and COVID-19 Research
- Nonlinear Dynamics and Pattern Formation
- Drug-Induced Hepatotoxicity and Protection
- vaccines and immunoinformatics approaches
- Virology and Viral Diseases
- Micro and Nano Robotics
- Protein purification and stability
- Computational Drug Discovery Methods
- Plant Virus Research Studies
- Cardiomyopathy and Myosin Studies
Program for Appropriate Technology in Health
2024
National Institute of Allergy and Infectious Diseases
2017-2024
National Institutes of Health
2017-2024
University of California, Los Angeles
2009-2018
National Institute of Biomedical Research
2007-2016
University of California System
2010
Studies on the burden of human monkeypox in Democratic Republic Congo (DRC) were last conducted from 1981 to 1986. Since then, population that is immunologically naïve orthopoxviruses has increased significantly due cessation mass smallpox vaccination campaigns. To assess current risk infection, we analyzed incidence trends a monkeypox-enzootic region. Active, population-based surveillance was nine health zones central DRC. Epidemiologic data and biological samples obtained suspected cases....
Antibodies block Ebola virus entry The recent outbreak in West Africa illustrates the need for both an effective vaccine and therapies to treat infected individuals. Corti et al. isolated two monoclonal antibodies from a survivor of 1995 Kikwit demonstrated their therapeutic efficacy virus–infected macaques. In fact, one antibody protected macaques when it was given up 5 days after infection. Misasi solved crystal structures fragments bound glycoprotein (GP), which mediates viral cell entry....
Abstract Monkeypox virus is a zoonotic endemic to Central Africa. Although active disease surveillance has assessed monkeypox prevalence and geographic range, information about diversity lacking. We therefore genome of viruses in 60 samples obtained from humans with primary secondary cases infection 2005 through 2007. detected 4 distinct lineages deletion that resulted gene loss 10 (16.7%) seemed correlate human-to-human transmission (p = 0.0544). The data suggest high frequency spillover...
New approaches for the prevention and elimination of malaria, a leading cause illness death among infants young children globally, are needed.We conducted phase 1 clinical trial to assess safety pharmacokinetics L9LS, next-generation antimalarial monoclonal antibody, its protective efficacy against controlled human malaria infection in healthy adults who had never or received vaccine malaria. The participants L9LS either intravenously subcutaneously at dose mg, 5 20 mg per kilogram body...
CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in phase 1 clinical trial. Whether can prevent P. region which the endemic unknown.We conducted 2 trial assess safety and efficacy of single intravenous infusion healthy adults Mali over 6-month malaria season. In Part A, assessed at three escalating dose levels. B, participants were randomly assigned (in 1:1:1 ratio) receive 10 mg per kilogram body weight, 40 kilogram, or placebo....
By analyzing vesicle fluids and crusted scabs from 136 persons with suspected monkeypox, we identified 51 cases of monkeypox by PCR, sequenced the hemagglutinin gene, confirmed 94% virus culture. PCR demonstrated chickenpox in 61 patients. Coinfection both viruses was found 1 additional patient.
Additional interventions are needed to reduce the morbidity and mortality caused by malaria.
Although the incidence of human monkeypox has greatly increased in Central Africa over last decade, resources for surveillance remain extremely limited. We conducted a geospatial analysis using existing data to better inform future efforts. Using active collected between 2005 and 2007, we identified locations Sankuru district, Democratic Republic Congo (DRC) where there have been one or more cases monkeypox. To assess what taxa constitute main reservoirs monkeypox, tested whether were...
Trypanosoma brucei , a parasitic protist with single flagellum, is the causative agent of African sleeping sickness. Propulsion T. was long believed to be by drill-like, helical motion. Using millisecond differential interference-contrast microscopy and analyzing image sequences cultured procyclic-form bloodstream-form parasites, as well cells in infected mouse blood, we find that, instead, motility propagation kinks, separating left-handed right-handed waves. Kink-driven motility,...
African trypanosomes, Trypanosoma brucei spp., are lethal pathogens that cause substantial human suffering and limit economic development in some of the world's most impoverished regions. The name ("auger cell") derives from parasite's distinctive motility, which is driven by a single flagellum. However, despite decades study, requirement for trypanosome motility mammalian host infection has not been established. LC1 conserved dynein subunit required flagellar motility. Prior studies with...
Climate change is predicted to result in changes the geographic ranges and local prevalence of infectious diseases, either through direct effects on pathogen, or indirectly range shifts vector reservoir species. To better understand occurrence monkeypox virus (MPXV), an emerging Orthopoxvirus humans, under contemporary future climate conditions, we used ecological niche modeling techniques conjunction with remote-sensing variables. We first created spatially explicit probability...
Previous studies suggest that cases of Ebola virus disease (EVD) may go unreported because they are asymptomatic or unrecognized, but evidence is limited by study designs and sample size.A large population-based survey was conducted (n = 3415) to assess animal exposures behaviors associated with Ebolavirus antibody prevalence in rural Kasai Oriental province the Democratic Republic Congo (DRC). Fourteen villages were randomly selected all healthy individuals ≥1 year age eligible.Overall, 11%...
Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting might be improved has unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) cell receptors used vaccination...
Combinations of monoclonal antibodies (mAbs) against different epitopes on the same antigen synergistically neutralize many viruses. However, there are limited studies assessing whether combining human mAbs distinct regions Plasmodium falciparum (Pf) circumsporozoite protein (CSP) enhances in vivo protection malaria compared to each mAb alone or passive transfer PfCSP would improve following vaccination PfCSP. Here, we isolated a panel subdominant C-terminal domain (C-CSP) from volunteer...
The flagellum of Trypanosoma brucei is an essential and multifunctional organelle that receiving increasing attention as a potential drug target system for studying biology. RNA interference (RNAi) knockdown widely used to test the requirement protein in flagellar motility has suggested normal viability bloodstream-form trypanosomes. However, RNAi alone provides limited functional information because consequence often loss multiprotein complex. We therefore developed inducible allows...
CIS43 is a potent neutralizing human mAb that targets highly conserved "junctional" epitope in the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP). Enhancing durability of vivo will be important for clinical translation. Here, 2 approaches were used to improve while maintaining neutralization. First, Fc domain was modified with LS mutations (CIS43LS) increase binding affinity neonatal receptor (FcRn). CIS43LS and showed comparable protective efficacy. had 9- 13-fold increased...
Rare and potent monoclonal antibodies (mAbs) against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) on infective sporozoites (SPZ) preferentially bind PfCSP junctional tetrapeptide NPDP or NVDP minor repeats while cross-reacting with NANP central in vitro. The extent to which each of these epitopes is required for protection vivo unknown. Here, we assessed whether junction-, repeat- repeat-preferring human mAbs (CIS43, L9 317 respectively) bound protected challenge transgenic...
The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance potency clinical utility of CIS43, we used iterative site-saturation mutagenesis DNA shuffling screen precise gene-variant yeast display libraries improved PfCSP antigen recognition. We identified several mutations that recognition, predominately framework regions, combined these...