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  1. Article ; Online: Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates

    Yi-Nan Zhang / Jennifer Paynter / Aleksandar Antanasijevic / Joel D. Allen / Mor Eldad / Yi-Zong Lee / Jeffrey Copps / Maddy L. Newby / Linling He / Deborah Chavez / Pat Frost / Anna Goodroe / John Dutton / Robert Lanford / Christopher Chen / Ian A. Wilson / Max Crispin / Andrew B. Ward / Jiang Zhu

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 29

    Abstract: Abstract Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We ... ...

    Abstract Abstract Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. For 1c-SApNPs, glycan trimming improves recognition of the CD4 binding site without affecting broadly neutralizing antibodies (bNAbs) to major glycan epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increases the frequency of vaccine responders (FVR) and steers antibody responses away from immunodominant glycan holes and glycan patches. The mechanism of vaccine-induced immunity is examined in mice. Compared with the UFO trimer, the multilayered E2p and I3-01v9 1c-SApNPs show 420 times longer retention in lymph node follicles, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions. These findings can inform future HIV-1 vaccine development.
    Keywords Science ; Q
    Subject code 570
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies

    Hailee R. Perrett / Philip J.M. Brouwer / Jonathan Hurtado / Maddy L. Newby / Lin Liu / Helena Müller-Kräuter / Sarah Müller Aguirre / Judith A. Burger / Joey H. Bouhuijs / Grace Gibson / Terrence Messmer / John S. Schieffelin / Aleksandar Antanasijevic / Geert-Jan Boons / Thomas Strecker / Max Crispin / Rogier W. Sanders / Bryan Briney / Andrew B. Ward

    Cell Reports, Vol 42, Iss 5, Pp 112524- (2023)

    2023  

    Abstract: Summary: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable ... ...

    Abstract Summary: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
    Keywords CP: Immunology ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Sensitive Detection of SARS-CoV-2–Specific Antibodies in Dried Blood Spot Samples

    Gabriella L. Morley / Stephen Taylor / Sian Jossi / Marisol Perez-Toledo / Sian E. Faustini / Edith Marcial-Juarez / Adrian M. Shields / Margaret Goodall / Joel D. Allen / Yasunori Watanabe / Maddy L. Newby / Max Crispin / Mark T. Drayson / Adam F. Cunningham / Alex G. Richter / Matthew K. O’Shea

    Emerging Infectious Diseases, Vol 26, Iss 12, Pp 2970-

    2020  Volume 2973

    Abstract: Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS ... ...

    Abstract Dried blood spot (DBS) samples can be used for the detection of severe acute respiratory syndrome coronavirus 2 spike antibodies. DBS sampling is comparable to matched serum samples with a relative 98.1% sensitivity and 100% specificity. Thus, DBS sampling offers an alternative for population-wide serologic testing in the coronavirus pandemic.
    Keywords COVID-19 ; coronavirus disease ; SARS-CoV-2 ; severe acute respiratory syndrome coronavirus 2 ; viruses ; respiratory infections ; Medicine ; R ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Centers for Disease Control and Prevention
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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