31 Result(s)
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Article
Engineering immune evasion
One obstacle to realizing the promise of viral vectors for vaccine delivery is pre-existing immunity to such vectors. An adroit application of structure-based design points to a way around that problem.
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Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9
Variable regions 1 and 2 (V1/V2) of human immunodeficiency virus-1 (HIV-1) gp120 envelope glycoprotein are critical for viral evasion of antibody neutralization, and are themselves protected by extraordinary s...
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Article
Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals,...
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Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies
Antibodies capable of neutralizing HIV-1 often target variable regions 1 and 2 (V1V2) of the HIV-1 envelope, but the mechanism of their elicitation has been unclear. Here we define the developmental pathway by...
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Open AccessPrimate immune responses to HIV-1 Env formulated in the saponin-based adjuvant AbISCO-100 in the presence or absence of TLR9 co-stimulation
Protein-based vaccines require adjuvants to achieve optimal responses. Toll-like receptor (TLR) 9 agonists were previously shown to improve responses to protein-based vaccines, such as the Hepatitis B virus va...
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Open AccessAnalysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization
Develo** predictive animal models to assess how candidate vaccines and infection influence the ontogenies of Envelope (Env)-specific antibodies is critical for the development of an HIV vaccine. Here we use ...
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Open AccessEvaluation of candidate vaccine approaches for MERS-CoV
The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely...
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Open AccessActivation and lysis of human CD4 cells latently infected with HIV-1
The treatment of AIDS with combination antiretroviral therapy (cART) remains lifelong largely because the virus persists in latent reservoirs. Elimination of latently infected cells could therefore reduce trea...
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Open AccessHIV-1 Vaccine-elicited Antibodies Reverted to Their Inferred Naive Germline Reveal Associations between Binding Affinity and in vivo Activation
The elicitation of HIV-1 broadly neutralizing antibodies following envelope glycoprotein (Env) vaccination is exceedingly difficult. Suboptimal engagement of naïve B cells is suggested to limit these low frequ...
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Article
Open AccessReconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation
Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to id...
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Article
Open AccessInitiation of HIV neutralizing B cell lineages with sequential envelope immunizations
A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host toleranc...
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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...
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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...
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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...
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Open AccessImprovement of antibody functionality by structure-guided paratope engraftment
Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding...
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Open AccessDifficult-to-neutralize global HIV-1 isolates are neutralized by antibodies targeting open envelope conformations
The HIV-1 envelope (Env) is the target for neutralizing antibodies and exists on the surface of virions in open or closed conformations. Difficult-to-neutralize viruses (tier 2) express Env in a closed conform...
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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...
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Open AccessSingle-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity
Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously...
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Open AccessGlycan repositioning of influenza hemagglutinin stem facilitates the elicitation of protective cross-group antibody responses
The conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; h...
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Open AccessImmune checkpoint modulation enhances HIV-1 antibody induction
Eliciting protective titers of HIV-1 broadly neutralizing antibodies (bnAbs) is a goal of HIV-1 vaccine development, but current vaccine strategies have yet to induce bnAbs in humans. Many bnAbs isolated from ...
