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  1. AU="Rubsamen, Michael"
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  1. Article ; Online: Analysis of well-annotated next-generation sequencing data reveals increasing cases of SARS-CoV-2 reinfection with Omicron.

    Burkholz, Scott / Rubsamen, Michael / Blankenberg, Luke / Carback, Richard T / Mochly-Rosen, Daria / Harris, Paul E

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 288

    Abstract: SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non-Omicron VOC. An ...

    Abstract SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non-Omicron VOC. An analysis of the sub-lineages associated with an Omicron primary infection and Omicron reinfection reveals that the incidence of Omicron-Omicron reinfections is occurring over a shorter time interval than seen after a primary infection with a non-Omicron VOC. Our analysis suggests that a single infection from SARS-CoV-2 may not generate the protective immunity required to defend against reinfections from emerging Omicron lineages. This analysis was made possible by Next-generation sequencing (NGS) of a Danish cohort with clinical metadata on both infections occurring in the same individual. We suggest that the continuation of COVID-19 NGS and inclusion of clinical metadata is necessary to ensure effective surveillance of SARS-CoV-2 genomics, assist in treatment and vaccine development, and guide public health recommendations.
    MeSH term(s) Humans ; SARS-CoV-2/genetics ; COVID-19 ; Reinfection ; High-Throughput Nucleotide Sequencing ; Genomics
    Language English
    Publishing date 2023-03-18
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-04687-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Adjuvant AS01 activates human monocytes for costimulation and systemic inflammation.

    Smith, Carson L / Richardson, Brian / Rubsamen, Michael / Cameron, Mark J / Cameron, Cheryl M / Canaday, David H

    Vaccine

    2023  Volume 42, Issue 2, Page(s) 229–238

    Abstract: Background: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of ...

    Abstract Background: The adjuvanted recombinant zoster vaccine (RZV) is highly effective even in adults over 80 years old. The high efficacy of RZV is attributed to its highly reactogenic adjuvant, AS01, but limited studies have been done on AS01's activation of human immune cells.
    Methods: We stimulated peripheral blood mononuclear cells (PBMC) with AS01 and used flow cytometry and RNA Sequencing (RNAseq) to analyze the impacts on human primary cells.
    Results: We found that incubation of PBMC with AS01 activated monocytes to a greater extent than any other cell population, including dendritic cells. Both classical and non-classical monocytes demonstrated this activation. RNASeq showed that TNF-ɑ and IL1R pathways were highly upregulated in response to AS01 exposure, even in older adults.
    Conclusions: In a PBMC co-culture, AS01 strongly activates human monocytes to upregulate costimulation markers and induce cytokines that mediate systemic inflammation. Understanding AS01's impacts on human cells opens possibilities to further address the reduced vaccine response associated with aging.
    MeSH term(s) Humans ; Aged ; Aged, 80 and over ; Leukocytes, Mononuclear ; Monocytes ; Adjuvants, Immunologic/pharmacology ; Herpes Zoster/prevention & control ; Vaccines, Synthetic ; Herpes Zoster Vaccine ; Inflammation
    Chemical Substances Adjuvants, Immunologic ; Vaccines, Synthetic ; Herpes Zoster Vaccine
    Language English
    Publishing date 2023-12-07
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 605674-x
    ISSN 1873-2518 ; 0264-410X
    ISSN (online) 1873-2518
    ISSN 0264-410X
    DOI 10.1016/j.vaccine.2023.12.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Increasing Cases of SARS-CoV-2 Omicron Reinfection Reveals Ineffective Post-COVID-19 Immunity in Denmark and Conveys the Need for Continued Next-Generation Sequencing

    Burkholz, Scott / Rubsamen, Michael / Blankenburg, Luke / Carback, Richard Thomas / Mochly-Rosen, Daria / Harris, Paul E

    medRxiv

    Abstract: Abstract SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non- ... ...

    Abstract Abstract SARS-CoV-2 has extensively mutated creating variants of concern (VOC) resulting in global infection surges. The Omicron VOC reinfects individuals exposed to earlier variants of SARS-CoV-2 at a higher frequency than previously seen for non-Omicron VOC. An analysis of the sub-lineages associated with an Omicron primary infection and Omicron reinfection reveals that the incidence of Omicron-Omicron reinfections is occurring over a shorter time interval than seen after a primary infection with a non-Omicron VOC. Our analysis suggests that a single infection from SARS-CoV-2 may not generate the protective immunity required to defend against reinfections from emerging Omicron lineages. This analysis was made possible by Next-generation sequencing (NGS), specifically of a Danish cohort with clinical metadata on both infections occurring in the same individual. We suggest that the continuation of COVID-19 NGS and inclusion of clinical metadata is necessary to ensure effective surveillance of SARS-CoV-2 genomics, assist in treatment and vaccine development, and guide public health recommendations.
    Keywords covid19
    Language English
    Publishing date 2022-09-14
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2022.09.13.22279912
    Database COVID19

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  4. Article: Activated NK Cells with Pro-inflammatory Features are Associated with Atherogenesis in Perinatally HIV-Acquired Adolescents.

    Alles, Mario / Gunasena, Manuja / Kettelhut, Aaren / Ailstock, Kate / Musiime, Victor / Kityo, Cissy / Richardson, Brian / Mulhern, Will / Tamilselvan, Banumathi / Rubsamen, Michael / Kasturiratna, Dhanuja / Demberg, Thorsten / Cameron, Cheryl M / Cameron, Mark J / Dirajlal-Fargo, Sahera / Funderburg, Nicholas T / Liyanage, Namal P M

    medRxiv : the preprint server for health sciences

    2023  

    Abstract: Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co- ... ...

    Abstract Human immunodeficiency virus (HIV) is associated with persistent immune activation and dysfunction in people with HIV despite treatment with antiretroviral therapy (ART). Modulation of the immune system may be driven by: low-level HIV replication, co-pathogens, gut dysbiosis /translocation, altered lipid profiles, and ART toxicities. In addition, perinatally acquired HIV (PHIV) and lifelong ART may alter the development and function of the immune system. Our preliminary data and published literature suggest reprogramming innate immune cells may accelerate aging and increase the risk for future end-organ complications, including cardiovascular disease (CVD). The exact mechanisms, however, are currently unknown. Natural killer (NK) cells are a highly heterogeneous cell population with divergent functions. They play a critical role in HIV transmission and disease progression in adults. Recent studies suggest the important role of NK cells in CVDs; however, little is known about NK cells and their role in HIV-associated cardiovascular risk in PHIV adolescents. Here, we investigated NK cell subsets and their potential role in atherogenesis in PHIV adolescents compared to HIV-negative adolescents in Uganda. Our data suggest, for the first time, that activated NK subsets in PHIV adolescents may contribute to atherogenesis by promoting plasma oxidized low-density lipoprotein (Ox-LDL) uptake by vascular macrophages.
    Language English
    Publishing date 2023-11-07
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.11.06.23297580
    Database MEDical Literature Analysis and Retrieval System OnLINE

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