A5065160556- Viral Infections and Outbreaks Research
- Hepatitis B Virus Studies
- Viral Infections and Vectors
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Bacillus and Francisella bacterial research
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Immune Cell Function and Interaction
- Respiratory viral infections research
- T-cell and B-cell Immunology
- Vector-Borne Animal Diseases
- Influenza Virus Research Studies
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Vaccine Coverage and Hesitancy
- Herpesvirus Infections and Treatments
Scripps Institution of Oceanography
2020-2024
San Diego Biomedical Research Institute
2024
Scripps Research Institute
2013-2022
International AIDS Vaccine Initiative
2013-2014
PG9 is the founder member of an expanding family glycan-dependent human antibodies that preferentially bind HIV (HIV-1) envelope (Env) glycoprotein (gp) trimer and broadly neutralize virus. Here, we show a soluble SOSIP.664 gp140 constructed from Clade A BG505 sequence binds with high affinity (∼11 nM), enabling structural biophysical characterizations PG9:Env complex. The remarkably stable as assessed by electron microscopy (EM) differential scanning calorimetry. EM, small angle X-ray...
Profiling the antibody response to Ebola The recent virus outbreak in West Africa illustrates need not only for a vaccine but potential therapies, too. One promising therapy is monoclonal antibodies that target Ebola's membrane-anchored glycoprotein (GP). Bornholdt et al. isolated and characterized 349 from survivor of 2014 outbreak. A large fraction showed some neutralizing activity several were quite potent. Structural analysis revealed an important site vulnerability on membrane stalk...
Significance Ebola virus causes lethal hemorrhagic fever, and the current 2014 outbreak in western Africa is largest on record to date. No vaccines or therapeutics are yet approved for human use. Therapeutic antibody cocktails, however, have shown efficacy against otherwise infection show significant promise eventual Here we provide structures of every mAb ZMapp cocktail, as well additional antibodies from MB-003 ZMAb cocktails which was derived, each complex with glycoprotein. The set...
For most classes of drugs, rapid development therapeutics to treat emerging infections is challenged by the timelines needed identify compounds with desired efficacy, safety, and pharmacokinetic profiles. Fully human monoclonal antibodies (mAbs) provide an attractive method overcome many these hurdles rapidly produce for diseases. In this study, we deployed a platform generate, test, develop fully Zaire ebolavirus. We obtained specific anti-Ebola virus (EBOV) immunizing VelocImmune mice that...
Previous efforts to identify cross-neutralizing antibodies the receptor-binding site (RBS) of ebolavirus glycoproteins have been unsuccessful, largely because RBS is occluded on viral surface. We report a monoclonal antibody (FVM04) that targets uniquely exposed epitope within RBS; cross-neutralizes Ebola (EBOV), Sudan (SUDV), and, lesser extent, Bundibugyo viruses; and shows protection against EBOV SUDV in mice guinea pigs. The cocktail ZMapp™ remarkably effective (Zaire) but does not...
The neutralizing anti-HIV-1 antibody 2G12 is of particular interest due to the sterilizing protection it provides from viral challenge in animal models. a unique, domain-exchanged that binds exclusively conserved N-linked glycans form high-mannose patch on gp120 outer domain centered glycan at position N332. Several and around epitope have been shown interact with other potent, broadly antibodies; therefore, this region constitutes supersite vulnerability gp120. While crystal structures...
The filoviruses, which include the marburg- and ebolaviruses, have caused multiple outbreaks among humans this decade. Antibodies against filovirus surface glycoprotein (GP) been shown to provide life-saving therapy in nonhuman primates, but such antibodies are generally virus-specific. Many monoclonal (mAbs) described Ebola virus. In contrast, relatively few Marburg Here we present ten mAbs elicited by immunization of mice using recombinant mucin-deleted GPs from different virus (MARV)...
Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in adaptive response of survivors. A subset is known to be broadly neutralizing, but details their epitopes and basis for neutralization not well understood. Here, we present cryoelectron microscopy (cryo-EM) structures diverse antibodies variably synergize with GP base-binding antibodies. These describe a conserved site vulnerability anchors mucin-like domains (MLDs) cap, which call MLD anchor cradle....
Monoclonal antibodies (mAbs) with pan-ebolavirus cross-reactivity are highly desirable, but development of such mAbs is limited by a lack molecular understanding cross-reactive epitopes. The antibody ADI-15878 was previously identified from human survivor Ebola virus Makona variant (EBOV/Mak) infection. This mAb demonstrated potent neutralizing activity against all known ebolaviruses and provided protection in rodent ferret models three ebolavirus species. Here, we describe the unliganded...
Abstract Natural Killer (NK) cells utilize effector functions, including antibody-dependent cellular cytotoxicity (ADCC), for the clearance of viral infection and malignancies. NK cell ADCC is mediated by Fc γ RIIIa (CD16a) binding to fragment crystallizable (Fc) region immunoglobulin G (IgG) within immune complexes on a target surface. While antibody-induced clustering CD16a thought drive ADCC, molecular basis this activity has not been fully described. Here we use MINFLUX nanoscopy map...
Summary Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in adaptive response of survivors. A subset is known to be broadly neutralizing, but details their epitopes and basis for neutralization not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures several antibodies variably synergize with GP base-binding antibodies. These describe a conserved site vulnerability anchors mucin-like domains (MLD) cap, which name MLD-anchor...