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Article
The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes
Although human immunodeficiency virus-1 (HIV-1) infects quiescent and proliferating CD4+ lymphocytes, the virus replicates poorly in resting T cells1,2,3,4,5,6. Factors that block viral replication in these cells...
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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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Article
Allied responses
The main function of neutralizing antibodies is to block viral entry into host cells. But, for maximal protection against HIV, such antibodies must call upon other elements of the immune system to help with th...
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Article
Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals
Serologic memory is an important factor in long-term vaccine efficacy, but there is little understanding of the antibodies produced by memory B cells in individuals infected with important human pathogens such...
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Article
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
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody
Characterization of human monoclonal antibodies is providing considerable insight into mechanisms of broad HIV-1 neutralization. Here we report an HIV-1 gp41 membrane-proximal external region (MPER)-specific a...
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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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Article
Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with si...
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Article
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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Article
Enhanced neonatal Fc receptor function improves protection against primate SHIV infection
A mutation in VRC01, a broadly neutralizing, HIV-1-specific antibody, confers enhanced binding to the neonatal Fc receptor, increasing the antibody half-life in the serum and localization in mucosal tissues, w...
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Article
Structure and immune recognition of trimeric pre-fusion HIV-1 Env
The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unlig...
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Article
Broad and potent HIV-1 neutralization by a human antibody that binds the gp41–gp120 interface
Molecular and structural characterization is reported for a new broad and potent monoclonal antibody against HIV that binds to an epitope bridging the gp41 and gp120 subunits — the antibody affects a step in v...
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Article
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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Article
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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Article
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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Article
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
A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges
A single injection of four anti-HIV-1-neutralizing monoclonal antibodies blocks repeated weekly low-dose virus challenges of simian/human immunodeficiency virus.
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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...