27 Result(s)
within
Nicole A. Doria-Rose
-
Article
Open AccessRAIN: machine learning-based identification for HIV-1 bNAbs
Broadly neutralizing antibodies (bNAbs) are promising candidates for the treatment and prevention of HIV-1 infections. Despite their critical importance, automatic detection of HIV-1 bNAbs from immune repertoi...
-
Article
Open AccessHuman CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains
The vaccine elicitation of HIV tier-2-neutralization antibodies has been a challenge. Here, we report the isolation and characterization of a CD4-binding site (CD4bs) specific monoclonal antibody, HmAb64, from...
-
Article
Open AccessAntibody-directed evolution reveals a mechanism for enhanced neutralization at the HIV-1 fusion peptide site
The HIV-1 fusion peptide (FP) represents a promising vaccine target, but global FP sequence diversity among circulating strains has limited anti-FP antibodies to ~60% neutralization breadth. Here we evolve the...
-
Article
Open AccessTrispecific antibody targeting HIV-1 and T cells activates and eliminates latently-infected cells in HIV/SHIV infections
Agents that can simultaneously activate latent HIV, increase immune activation and enhance the killing of latently-infected cells represent promising approaches for HIV cure. Here, we develop and evaluate a tr...
-
Article
Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Omicron lineage has resulted in diminished Coronavirus Disease 2019 (COVID-19) vaccine efficacy and persistent tran...
-
Article
Open AccessPrimary exposure to SARS-CoV-2 variants elicits convergent epitope specificities, immunoglobulin V gene usage and public B cell clones
An important consequence of infection with a SARS-CoV-2 variant is protective humoral immunity against other variants. However, the basis for such cross-protection at the molecular level is incompletely unders...
-
Article
Open AccessEngineering of HIV-1 neutralizing antibody CAP256V2LS for manufacturability and improved half life
The broadly neutralizing antibody (bNAb) CAP256-VRC26.25 has exceptional potency against HIV-1 and has been considered for clinical use. During the characterization and production of this bNAb, we observed sev...
-
Article
Open AccessTyrosine O-sulfation proteoforms affect HIV-1 monoclonal antibody potency
CAP256V2LS, a broadly neutralizing monoclonal antibody (bNAb), is being pursued as a promising drug for HIV-1 prevention. The total level of tyrosine-O-sulfation, a post-translational modification, was known to p...
-
Article
Defining the risk of SARS-CoV-2 variants on immune protection
The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced after infection or vaccination. To address the public he...
-
Article
Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial
Adeno-associated viral vector-mediated transfer of DNA coding for broadly neutralizing anti-HIV antibodies (bnAbs) offers an alternative to attempting to induce protection by vaccination or by repeated infusio...
-
Article
Open AccessExtended antibody-framework-to-antigen distance observed exclusively with broad HIV-1-neutralizing antibodies recognizing glycan-dense surfaces
Antibody-Framework-to-Antigen Distance (AFAD) – the distance between the body of an antibody and a protein antigen – is an important parameter governing antibody recognition. Here, we quantify AFAD for ~2,000 ...
-
Article
SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness
A vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to control the coronavirus disease 2019 (COVID-19) global pandemic. Structural studies have led to the development of mutati...
-
Article
Open AccessPreclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen
The vaccine elicitation of broadly neutralizing antibodies against HIV-1 is a long-sought goal. We previously reported the amino-terminal eight residues of the HIV-1-fusion peptide (FP8) – when conjugated to t...
-
Article
Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor
Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of elici...
-
Article
Open AccessAccurate Prediction for Antibody Resistance of Clinical HIV-1 Isolates
Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) have promising utility in prevention and treatment of HIV-1 infection, and several are currently undergoing clinical tria...
-
Article
Open AccessLattice engineering enables definition of molecular features allowing for potent small-molecule inhibition of HIV-1 entry
Diverse entry inhibitors targeting the gp120 subunit of the HIV-1 envelope (Env) trimer have been developed including BMS-626529, also called temsavir, a prodrug version of which is currently in phase III clin...
-
Article
Open AccessSequencing HIV-neutralizing antibody exons and introns reveals detailed aspects of lineage maturation
The developmental pathways of broadly neutralizing antibodies (bNAbs) against HIV are of great importance for the design of immunogens that can elicit protective responses. Here we show the maturation features...
-
Article
Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1
A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residue...
-
Article
Open AccessRational design of a trispecific antibody targeting the HIV-1 Env with elevated anti-viral activity
HIV-1 broadly neutralizing antibodies (bNAbs) are being explored as passively administered therapeutic and preventative agents. However, the extensively diversified HIV-1 envelope glycoproteins (Env) rapidly a...
-
Article
Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design
Crystal structures of HIV-1 Env V1V2 in complex with human broadly neutralizing antibodies and ontogeny analyses allow the engineering of Env trimers that are recognized by ancestor and intermediate antibody f...
