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  1. Article ; Online: Activation of coagulation and proinflammatory pathways in thrombosis with thrombocytopenia syndrome and following COVID-19 vaccination

    Malika Aid / Kathryn E. Stephenson / Ai-ris Y. Collier / Joseph P. Nkolola / James V. Michael / Steven E. McKenzie / Dan H. Barouch

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

    2023  Volume 10

    Abstract: Abstract Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS ...

    Abstract Abstract Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15–19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk.
    Keywords Science ; Q
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: HIV Antibody Fc N-Linked Glycosylation Is Associated with Viral Rebound

    Rasmus Offersen / Wen-Han Yu / Eileen P. Scully / Boris Julg / Zelda Euler / Saheli Sadanand / Dario Garcia-Dominguez / Lu Zheng / Thomas A. Rasmussen / Madeleine F. Jennewein / Caitlyn Linde / Jessica Sassic / Giuseppe Lofano / Selena Vigano / Kathryn E. Stephenson / Stephanie Fischinger / Todd J. Suscovich / Mathias Lichterfeld / Douglas Lauffenburger /
    Erik S. Rosenberg / Todd Allen / Marcus Altfeld / Richelle C. Charles / Lars Østergaard / Martin Tolstrup / Dan H. Barouch / Ole S. Søgaard / Galit Alter

    Cell Reports, Vol 33, Iss 11, Pp 108502- (2020)

    2020  

    Abstract: Summary: Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with ... ...

    Abstract Summary: Changes in antibody glycosylation are linked to inflammation across several diseases. Alterations in bulk antibody galactosylation can predict rheumatic flares, act as a sensor for immune activation, predict gastric cancer relapse, track with biological age, shift with vaccination, change with HIV reservoir size on therapy, and decrease in HIV and HCV infections. However, whether changes in antibody Fc biology also track with reservoir rebound time remains unclear. The identification of a biomarker that could forecast viral rebound time could significantly accelerate the downselection and iterative improvement of promising HIV viral eradication strategies. Using a comprehensive antibody Fc-profiling approach, the level of HIV-specific antibody Fc N-galactosylation is significantly associated with time to rebound after treatment discontinuation across three independent cohorts. Thus virus-specific antibody glycosylation may represent a promising, simply measured marker to track reservoir reactivation.
    Keywords HIV ; antibodies ; glycosylation ; viral host response ; biomarkers ; cure ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: First-in-human randomized controlled trial of an oral, replicating adenovirus 26 vector vaccine for HIV-1.

    Kathryn E Stephenson / Michael C Keefer / Catherine A Bunce / Doreen Frances / Peter Abbink / Lori F Maxfield / George H Neubauer / Joseph Nkolola / Lauren Peter / Christopher Lane / Harriet Park / Carl Verlinde / Angela Lombardo / Christopher Yallop / Menzo Havenga / Patricia Fast / John Treanor / Dan H Barouch

    PLoS ONE, Vol 13, Iss 11, p e

    2018  Volume 0205139

    Abstract: BACKGROUND:Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that ... ...

    Abstract BACKGROUND:Live, attenuated viral vectors that express HIV-1 antigens are being investigated as an approach to generating durable immune responses against HIV-1 in humans. We recently developed a replication-competent, highly attenuated Ad26 vector that expresses mosaic HIV-1 Env (rcAd26.MOS1.HIV-Env, "rcAd26"). Here we present the results of a first-in-human, placebo-controlled clinical trial to test the safety, immunogenicity and mucosal shedding of rcAd26 given orally. METHODS:Healthy adults were randomly assigned to receive a single oral dose of vaccine or placebo at 5:1 ratio in a dosage escalation of 10^8 to 10^11 rcAd26 VP (nominal doses) at University of Rochester Medical Center, Rochester, NY, USA. Participants were isolated and monitored for reactogenicity for 10 days post-vaccination, and adverse events were recorded up to day 112. Rectal and oropharyngeal secretions were evaluated for shedding of the vaccine. Humoral and cellular immune responses were measured. Household contacts were monitored for secondary vaccine transmission. RESULTS:We enrolled 22 participants and 11 household contacts between February 7 and June 24, 2015. 18 participants received one dose of HIV-1 vaccine and 4 participants received placebo. The vaccine caused only mild to moderate adverse events. No vaccine-related SAEs were observed. No infectious rcAd26 viral particles were detected in rectal or oropharyngeal secretions from any participant. Env-specific ELISA and ELISPOT responses were undetectable. No household contacts developed vaccine-induced HIV-1 seropositivity or vaccine-associated illness. CONCLUSIONS:The highly attenuated rcAd26.MOS1.HIV-Env vaccine was well tolerated up to 10^11 VP in healthy, HIV-1-uninfected adults, though the single dose was poorly immunogenic suggesting the replicative capacity of the vector was too attenuated. There was no evidence of shedding of infectious virus or secondary vaccine transmission following the isolation period. These data suggest the use of less attenuated viral vectors in ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2018-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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