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  1. Article ; Online: A 'mix and match' approach to SARS-CoV-2 vaccination.

    Deming, Meagan E / Lyke, Kirsten E

    Nature medicine

    2021  Volume 27, Issue 9, Page(s) 1510–1511

    MeSH term(s) COVID-19 ; COVID-19 Vaccines ; Humans ; SARS-CoV-2 ; Vaccination
    Chemical Substances COVID-19 Vaccines
    Language English
    Publishing date 2021-07-20
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1220066-9
    ISSN 1546-170X ; 1078-8956
    ISSN (online) 1546-170X
    ISSN 1078-8956
    DOI 10.1038/s41591-021-01463-x
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  2. Article ; Online: COVID-19 and Lessons to Be Learned from Prior Coronavirus Outbreaks.

    Deming, Meagan E / Chen, Wilbur H

    Annals of the American Thoracic Society

    2020  Volume 17, Issue 7, Page(s) 790–794

    MeSH term(s) Antiviral Agents/pharmacology ; Betacoronavirus/immunology ; Betacoronavirus/pathogenicity ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/physiopathology ; Coronavirus Infections/therapy ; Coronavirus Infections/virology ; Disease Transmission, Infectious/prevention & control ; Drug Development ; Global Health ; Humans ; Pandemics/prevention & control ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/therapy ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Viral Vaccines/pharmacology
    Chemical Substances Antiviral Agents ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-04-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2717461-X
    ISSN 2325-6621 ; 1943-5665 ; 2325-6621
    ISSN (online) 2325-6621 ; 1943-5665
    ISSN 2325-6621
    DOI 10.1513/AnnalsATS.202002-149PS
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  4. Article ; Online: Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Acquisition Is Associated With Individual Exposure but Not Community-Level Transmission.

    Friedman-Klabanoff, DeAnna J / Fitzpatrick, Meagan C / Deming, Meagan E / Agrawal, Vaidehi / Sitar, Sandra / Schaafsma, Torin / Brown, Elizabeth / Neuzil, Kathleen M / Barnabas, Ruanne V / Laufer, Miriam K

    The Journal of infectious diseases

    2022  Volume 226, Issue 2, Page(s) 225–235

    Abstract: Background: Transmission rates after exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individual within households and healthcare settings varies significantly between studies. Variability in the extent of exposure and ...

    Abstract Background: Transmission rates after exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive individual within households and healthcare settings varies significantly between studies. Variability in the extent of exposure and community SARS-CoV-2 incidence may contribute to differences in observed rates.
    Methods: We examined risk factors for SARS-CoV-2 infection in a randomized controlled trial of hydroxychloroquine as postexposure prophylaxis. Study procedures included standardized questionnaires at enrollment and daily self-collection of midturbinate swabs for SARS-CoV-2 polymerase chain reaction testing. County-level incidence was modeled using federally sourced data. Relative risks and 95% confidence intervals were calculated using modified Poisson regression.
    Results: Eighty-six of 567 (15.2%) household/social contacts and 12 of 122 (9.8%) healthcare worker contacts acquired SARS-CoV-2 infection. Exposure to 2 suspected index cases (vs 1) significantly increased risk for both household/social contacts (relative risk [RR], 1.86) and healthcare workers (RR, 8.18). Increased contact time also increased risk for healthcare workers (3-12 hours: RR, 7.82, >12 hours: RR, 11.81, vs ≤2 hours), but not for household/social contacts. County incidence did not impact risk.
    Conclusions: In our study, increased exposure to SARS-CoV-2 within household or healthcare settings led to higher risk of infection, but elevated community incidence did not. This reinforces the importance of interventions to decrease transmission in close contact settings.
    MeSH term(s) COVID-19/epidemiology ; Humans ; Hydroxychloroquine/adverse effects ; Post-Exposure Prophylaxis ; Risk Factors ; SARS-CoV-2
    Chemical Substances Hydroxychloroquine (4QWG6N8QKH)
    Language English
    Publishing date 2022-07-18
    Publishing country United States
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac029
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  5. Article ; Online: Accelerating Development of SARS-CoV-2 Vaccines - The Role for Controlled Human Infection Models.

    Deming, Meagan E / Michael, Nelson L / Robb, Merlin / Cohen, Myron S / Neuzil, Kathleen M

    The New England journal of medicine

    2020  Volume 383, Issue 10, Page(s) e63

    MeSH term(s) Betacoronavirus ; COVID-19 ; COVID-19 Vaccines ; Coronavirus Infections/prevention & control ; Human Experimentation/ethics ; Human Experimentation/standards ; Humans ; Pandemics/prevention & control ; Patient Safety ; Pneumonia, Viral/prevention & control ; Risk ; SARS-CoV-2 ; Viral Vaccines
    Chemical Substances COVID-19 Vaccines ; Viral Vaccines
    Keywords covid19
    Language English
    Publishing date 2020-07-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMp2020076
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  6. Article ; Online: A Novel Recombinant Influenza Virus Neuraminidase Vaccine Candidate Stabilized by a Measles Virus Phosphoprotein Tetramerization Domain Provides Robust Protection from Virus Challenge in the Mouse Model.

    Strohmeier, Shirin / Amanat, Fatima / Zhu, Xueyong / McMahon, Meagan / Deming, Meagan E / Pasetti, Marcela F / Neuzil, Kathleen M / Wilson, Ian A / Krammer, Florian

    mBio

    2021  Volume 12, Issue 6, Page(s) e0224121

    Abstract: Current seasonal influenza virus vaccines do not induce robust immune responses to neuraminidase. Several factors, including immunodominance of hemagglutinin over neuraminidase, instability of neuraminidase in vaccine formulations, and variable, ... ...

    Abstract Current seasonal influenza virus vaccines do not induce robust immune responses to neuraminidase. Several factors, including immunodominance of hemagglutinin over neuraminidase, instability of neuraminidase in vaccine formulations, and variable, nonstandardized amounts of neuraminidase in the vaccines, may contribute to this effect. However, vaccines that induce strong antineuraminidase immune responses would be beneficial, as they are highly protective. Furthermore, antigenic drift is slower for neuraminidase than for hemagglutinin, potentially providing broader coverage. Here, we designed stabilized recombinant versions of neuraminidase by replacing the N-terminal cytoplasmic domain, transmembrane, and extracellular stalk with tetramerization domains from the measles or Sendai virus phosphoprotein or from an Arabidopsis thaliana transcription factor. The measles virus tetramerization domain-based construct, termed N1-MPP, was chosen for further evaluation, as it retained antigenicity, neuraminidase activity, and structural integrity and provided robust protection
    MeSH term(s) Amino Acid Sequence ; Animals ; Antibodies, Viral/immunology ; Antigenic Drift and Shift ; Cross Reactions ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H1N1 Subtype/physiology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/chemistry ; Influenza Vaccines/genetics ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Influenza, Human/virology ; Measles virus/chemistry ; Measles virus/genetics ; Measles virus/immunology ; Mice ; Mice, Inbred BALB C ; Neuraminidase/administration & dosage ; Neuraminidase/chemistry ; Neuraminidase/genetics ; Neuraminidase/immunology ; Phosphoproteins/chemistry ; Phosphoproteins/genetics ; Phosphoproteins/immunology ; Protein Domains ; Sequence Alignment ; Vaccination ; Viral Proteins/administration & dosage ; Viral Proteins/chemistry ; Viral Proteins/genetics ; Viral Proteins/immunology
    Chemical Substances Antibodies, Viral ; Influenza Vaccines ; Phosphoproteins ; Viral Proteins ; NA protein, influenza A virus (EC 3.2.1.18) ; Neuraminidase (EC 3.2.1.18)
    Language English
    Publishing date 2021-11-23
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.02241-21
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  7. Article ; Online: Evaluation of a recombination-resistant coronavirus as a broadly applicable, rapidly implementable vaccine platform.

    Graham, Rachel L / Deming, Damon J / Deming, Meagan E / Yount, Boyd L / Baric, Ralph S

    Communications biology

    2018  Volume 1, Page(s) 179

    Abstract: Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks ...

    Abstract Emerging and re-emerging zoonotic viral diseases are major threats to global health, economic stability, and national security. Vaccines are key for reducing coronaviral disease burden; however, the utility of live-attenuated vaccines is limited by risks of reversion or repair. Because of their history of emergence events due to their prevalence in zoonotic pools, designing live-attenuated coronavirus vaccines that can be rapidly and broadly implemented is essential for outbreak preparedness. Here, we show that coronaviruses with completely rewired transcription regulatory networks (TRNs) are effective vaccines against SARS-CoV. The TRN-rewired viruses are attenuated and protect against lethal SARS-CoV challenge. While a 3-nt rewired TRN reverts via second-site mutation upon serial passage, a 7-nt rewired TRN is more stable, suggesting that a more extensively rewired TRN might be essential for avoiding growth selection. In summary, rewiring the TRN is a feasible strategy for limiting reversion in an effective live-attenuated coronavirus vaccine candidate that is potentially portable across the Nidovirales order.
    Keywords covid19
    Language English
    Publishing date 2018-10-29
    Publishing country England
    Document type Journal Article
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-018-0175-7
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  8. Article: Accelerating Development of SARS-CoV-2 Vaccines - The Role for Controlled Human Infection Models

    Deming, Meagan E / Michael, Nelson L / Robb, Merlin / Cohen, Myron S / Neuzil, Kathleen M

    N Engl J Med

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #621585
    Database COVID19

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  9. Article ; Online: Detection and Kinetics of Subgenomic Severe Acute Respiratory Syndrome Coronavirus 2 RNA Viral Load in Longitudinal Diagnostic RNA-Positive Samples.

    Deming, Meagan E / Dong, Tracy Q / Agrawal, Vaidehi / Mills, Margaret G / Huang, Meei Li W / Greninger, Alexander L / Jerome, Keith R / Wener, Mark H / Paasche-Orlow, Michael K / Kissinger, Patricia / Luk, Alfred / Hoffman, Risa M / Stewart, Jenell / Kottkamp, Angelica C / Bershteyn, Anna / Chu, Helen Y / Stankiewicz Karita, Helen C / Johnston, Christine M / Wald, Anna /
    Barnabas, Ruanne / Brown, Elizabeth R / Neuzil, Kathleen M

    The Journal of infectious diseases

    2022  Volume 226, Issue 5, Page(s) 788–796

    Abstract: While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are ... ...

    Abstract While detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by diagnostic reverse-transcription polymerase chain reaction (RT-PCR) is highly sensitive for viral RNA, the nucleic acid amplification of subgenomic RNAs (sgRNAs) that are the product of viral replication may more accurately identify replication. We characterized the diagnostic RNA and sgRNA detection by RT-PCR from nasal swab samples collected daily by participants in postexposure prophylaxis or treatment studies for SARS-CoV-2. Among 1932 RT-PCR-positive swab samples with sgRNA tests, 40% (767) had detectable sgRNA. Above a diagnostic RNA viral load (VL) threshold of 5.1 log10 copies/mL, 96% of samples had detectable sgRNA with VLs that followed a linear trend. The trajectories of diagnostic RNA and sgRNA VLs differed, with 80% peaking on the same day but duration of sgRNA detection being shorter (8 vs 14 days). With a large sample of daily swab samples we provide comparative sgRNA kinetics and a diagnostic RNA threshold that correlates with replicating virus independent of symptoms or duration of illness.
    MeSH term(s) COVID-19/diagnosis ; COVID-19 Testing ; Humans ; Kinetics ; RNA, Viral/analysis ; RNA, Viral/genetics ; SARS-CoV-2/genetics ; Viral Load
    Chemical Substances RNA, Viral
    Language English
    Publishing date 2022-02-15
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac048
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  10. Article: The SENIEUR protocol and the efficacy of hepatitis B vaccination in healthy elderly persons by age, gender, and vaccine route.

    Edelman, Robert / Deming, Meagan E / Toapanta, Franklin R / Heuser, Mark D / Chrisley, Lisa / Barnes, Robin S / Wasserman, Steven S / Blackwelder, William C / Handwerger, Barry S / Pasetti, Marcela / Siddiqui, Khan M / Sztein, Marcelo B

    Immunity & ageing : I & A

    2020  Volume 17, Page(s) 9

    Abstract: Background: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of ... ...

    Abstract Background: Reduced response to hepatitis B vaccines is associated with aging, confounding and comorbid conditions, as well as inadvertent subcutaneous (SC) inoculation. We hypothesized that the antibody and T cell-mediated immune responses (T-CMI) of elderly adults to a vaccine intended for intramuscular (IM) administration would be attenuated when deposited into SC fat, independent of confounding conditions.
    Results: Fifty-two healthy, community dwelling elderly adults (65-82 years), seronegative for HBV, were enrolled in the SENIEUR protocol as a strictly healthy population. These seniors were randomized to receive a licensed alum-adjuvanted recombinant HBV vaccine either SC or IM, with the inoculum site verified by imaging. The response rates, defined as hepatitis B surface antibodies (HBsAb) ≥10 IU/L, were significantly lower in the elderly than in young adults, a group of 12, healthy, 21-34-year-old volunteers. Moreover, elderly participants who received the vaccine IM were significantly more likely to be responders than those immunized SC (54% versus 16%,
    Conclusions: Our data demonstrate the blunted immunogenicity of SC inoculation as measured by peak titers and response rates. Further, the qualitative and quantitative deficits in B- and T-CMI responses to primary alum adjuvanted protein antigens persisted even in strictly healthy elderly populations with verified IM placement compared to younger populations.
    Clinical trial registration: ClinicalTrials.gov, NCT04162223. Registered 14 November 2019. Retrospectively registered.
    Keywords covid19
    Language English
    Publishing date 2020-04-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 2168941-6
    ISSN 1742-4933
    ISSN 1742-4933
    DOI 10.1186/s12979-020-00179-9
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