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Open AccessHeterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials
Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a...
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Open AccessCleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability
Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain i...
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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...
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Open AccessSelf-assembling SARS-CoV-2 spike-HBsAg nanoparticles elicit potent and durable neutralizing antibody responses via genetic delivery
While several COVID-19 vaccines have been in use, more effective and durable vaccines are needed to combat the ongoing COVID-19 pandemic. Here, we report highly immunogenic self-assembling SARS-CoV-2 spike-HBs...
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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...
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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...
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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...
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Open AccessSafety and antiviral activity of triple combination broadly neutralizing monoclonal antibody therapy against HIV-1: a phase 1 clinical trial
HIV-1 therapy with single or dual broadly neutralizing antibodies (bNAbs) has shown viral escape, indicating that at least a triple bNAb therapy may be needed for robust suppression of viremia. We performed a ...
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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...
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Open AccessFirst-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody
A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV l...
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A single residue in influenza virus H2 hemagglutinin enhances the breadth of the B cell response elicited by H2 vaccination
Conserved epitopes on the influenza hemagglutinin (HA) stem are an attractive target for universal vaccine strategies as they elicit broadly neutralizing antibodies. Such antibody responses to stem-specific ep...
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Safety and immunogenicity of a ferritin nanoparticle H2 influenza vaccine in healthy adults: a phase 1 trial
Currently, licensed seasonal influenza vaccines display variable vaccine effectiveness, and there remains a need for novel vaccine platforms capable of inducing broader responses against viral protein domains ...
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A multiclade env–gag VLP mRNA vaccine elicits tier-2 HIV-1-neutralizing antibodies and reduces the risk of heterologous SHIV infection in macaques
The development of a protective vaccine remains a top priority for the control of the HIV/AIDS pandemic. Here, we show that a messenger RNA (mRNA) vaccine co-expressing membrane-anchored HIV-1 envelope (Env) a...
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Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7
The COVID-19 pandemic has had widespread effects across the globe, and its causative agent, SARS-CoV-2, continues to spread. Effective interventions need to be developed to end this pandemic. Single and combin...
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Quadrivalent influenza nanoparticle vaccines induce broad protection
Influenza vaccines that confer broad and durable protection against diverse viral strains would have a major effect on global health, as they would lessen the need for annual vaccine reformulation and immuniza...
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Open AccessA comprehensive influenza reporter virus panel for high-throughput deep profiling of neutralizing antibodies
Broadly neutralizing antibodies (bnAbs) have been developed as potential countermeasures for seasonal and pandemic influenza. Deep characterization of these bnAbs and polyclonal sera provides pivotal understan...
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Open AccessA platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone
Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immu...
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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...
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Author Correction: Next-generation influenza vaccines: opportunities and challenges
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Next-generation influenza vaccines: opportunities and challenges
Seasonal influenza vaccines lack efficacy against drifted or pandemic influenza strains. Develo** improved vaccines that elicit broader immunity remains a public health priority. Immune responses to current ...