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  1. Article: Differences in the Clinical Manifestations and Host Immune Responses to SARS-CoV-2 Variants in Children Compared to Adults.

    Demirhan, Salih / Goldman, David L / Herold, Betsy C

    Journal of clinical medicine

    2023  Volume 13, Issue 1

    Abstract: The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, ... ...

    Abstract The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, clinical and epidemiological studies to understand the pathophysiology of this new family of viruses, which continues to evolve with the emergence of new genetic variants. One of the earliest clinical observations that provided a framework for the research was the finding that, in contrast to most other respiratory viruses, children developed less severe acute and post-acute disease compared to adults. Although the clinical manifestations of SARS-CoV-2 infection changed with each new wave of the pandemic, which was dominated by evolving viral variants, the differences in severity between children and adults persisted. Comparative immunologic studies have shown that children mount a more vigorous local innate response characterized by the activation of interferon pathways and recruitment of innate cells to the mucosa, which may mitigate against the hyperinflammatory adaptive response and systemic cytokine release that likely contributed to more severe outcomes including acute respiratory distress syndrome in adults. In this review, the clinical manifestations and immunologic responses in children during the different waves of COVID-19 are discussed.
    Language English
    Publishing date 2023-12-26
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662592-1
    ISSN 2077-0383
    ISSN 2077-0383
    DOI 10.3390/jcm13010128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Differences in the Clinical Manifestations and Host Immune Responses to SARS-CoV-2 Variants in Children Compared to Adults

    Salih Demirhan / David L. Goldman / Betsy C. Herold

    Journal of Clinical Medicine, Vol 13, Iss 1, p

    2023  Volume 128

    Abstract: The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, ... ...

    Abstract The COVID-19 pandemic challenged the medical field to rapidly identify and implement new approaches to the diagnosis, treatment and prevention of SARS-CoV-2 infections. The scientific community also needed to rapidly initiate basic, translational, clinical and epidemiological studies to understand the pathophysiology of this new family of viruses, which continues to evolve with the emergence of new genetic variants. One of the earliest clinical observations that provided a framework for the research was the finding that, in contrast to most other respiratory viruses, children developed less severe acute and post-acute disease compared to adults. Although the clinical manifestations of SARS-CoV-2 infection changed with each new wave of the pandemic, which was dominated by evolving viral variants, the differences in severity between children and adults persisted. Comparative immunologic studies have shown that children mount a more vigorous local innate response characterized by the activation of interferon pathways and recruitment of innate cells to the mucosa, which may mitigate against the hyperinflammatory adaptive response and systemic cytokine release that likely contributed to more severe outcomes including acute respiratory distress syndrome in adults. In this review, the clinical manifestations and immunologic responses in children during the different waves of COVID-19 are discussed.
    Keywords pediatric COVID-19 ; SARS-CoV-2 variants ; innate immunity ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: 50 Years Ago in The Journal of Pediatrics: Revisiting a Diagnostic Dilemma 50 Years Later: Partially Treated Bacterial Meningitis.

    Anosike, Brenda I / Herold, Betsy C

    The Journal of pediatrics

    2020  Volume 225, Page(s) 102

    MeSH term(s) Alaska ; Anti-Bacterial Agents/therapeutic use ; Child ; Escherichia coli ; Fever/cerebrospinal fluid ; Fever/diagnosis ; Fever/therapy ; Haemophilus influenzae ; History, 20th Century ; Humans ; Meningitis, Bacterial/cerebrospinal fluid ; Meningitis, Bacterial/diagnosis ; Meningitis, Bacterial/history ; Neisseria meningitidis ; Pediatrics/history ; Streptococcus pneumoniae
    Chemical Substances Anti-Bacterial Agents
    Language English
    Publishing date 2020-09-22
    Publishing country United States
    Document type Historical Article ; Journal Article
    ZDB-ID 3102-1
    ISSN 1097-6833 ; 0022-3476
    ISSN (online) 1097-6833
    ISSN 0022-3476
    DOI 10.1016/j.jpeds.2020.04.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Under-utilization of Narrow-Spectrum Antibiotics in the Ambulatory Management of Pediatric UTI: A Single-Center Experience.

    Lee, Philip / Kim, Mimi / Herold, Betsy C / Soma, Vijaya L

    Frontiers in pediatrics

    2021  Volume 9, Page(s) 675759

    Abstract: Objective: ...

    Abstract Objective:
    Language English
    Publishing date 2021-08-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2711999-3
    ISSN 2296-2360
    ISSN 2296-2360
    DOI 10.3389/fped.2021.675759
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: We Need to Address the Health of Children at the Border.

    Herold, Betsy C / Bryant, Kristina A

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2019  Volume 70, Issue 12, Page(s) 2724–2726

    MeSH term(s) Child ; Disease Outbreaks ; Humans ; Transients and Migrants
    Language English
    Publishing date 2019-09-19
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciz1029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Alphaherpesvirus Vaccines.

    Aschner, Clare Burn / Herold, Betsy C

    Current issues in molecular biology

    2020  Volume 41, Page(s) 469–508

    Abstract: Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of enormous preclinical and clinical research. A live viral vaccine for prevention of ... ...

    Abstract Prophylactic and therapeutic vaccines for the alphaherpesviruses including varicella zoster virus (VZV) and herpes simplex virus types 1 and 2 have been the focus of enormous preclinical and clinical research. A live viral vaccine for prevention of chickenpox and a subunit therapeutic vaccine to prevent zoster are highly successful. In contrast, progress towards the development of effective prophylactic or therapeutic vaccines against HSV-1 and HSV-2 has met with limited success. This review provides an overview of the successes and failures, the different types of immune responses elicited by various vaccine modalities, and the need to reconsider the preclinical models and immune correlates of protection against HSV.
    MeSH term(s) Alphaherpesvirinae/immunology ; Animals ; Herpesviridae Infections/immunology ; Herpesviridae Infections/prevention & control ; Humans ; Immunity/immunology ; Vaccines, Attenuated/immunology ; Vaccines, Subunit/immunology ; Viral Vaccines/immunology
    Chemical Substances Vaccines, Attenuated ; Vaccines, Subunit ; Viral Vaccines
    Language English
    Publishing date 2020-09-23
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2000024-8
    ISSN 1467-3045 ; 1467-3037
    ISSN (online) 1467-3045
    ISSN 1467-3037
    DOI 10.21775/cimb.041.469
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Author Correction: Cell-impermeable staurosporine analog targets extracellular kinases to inhibit HSV and SARS-CoV-2.

    Cheshenko, Natalia / Bonanno, Jeffrey B / Hoffmann, Hans-Heinrich / Jangra, Rohit K / Chandran, Kartik / Rice, Charles M / Almo, Steven C / Herold, Betsy C

    Communications biology

    2023  Volume 6, Issue 1, Page(s) 833

    Language English
    Publishing date 2023-08-10
    Publishing country England
    Document type Published Erratum
    ISSN 2399-3642
    ISSN (online) 2399-3642
    DOI 10.1038/s42003-023-05207-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Greater Durability and Protection against Herpes Simplex Viral Disease following Immunization of Mice with Single-Cycle ΔgD-2 Compared to an Adjuvanted Glycoprotein D Protein Vaccine.

    Mahant, Aakash Mahant / Gromisch, Matthew S / Kravets, Leah / Burn Aschner, Clare / Herold, Betsy C

    Vaccines

    2023  Volume 11, Issue 8

    Abstract: Herpes simplex viruses (HSV) cause chronic infections with significant morbidity. Prior vaccines, designed to generate neutralizing antibodies (nAbs) targeting glycoprotein D (gD), failed to provide durable protection. We adopted a different strategy and ...

    Abstract Herpes simplex viruses (HSV) cause chronic infections with significant morbidity. Prior vaccines, designed to generate neutralizing antibodies (nAbs) targeting glycoprotein D (gD), failed to provide durable protection. We adopted a different strategy and evaluated a single-cycle virus deleted in gD (ΔgD-2). ΔgD-2elicits antibodies that primarily mediate antibody-dependent cell mediated cytolysis (ADCC) and provides complete protection against clinical isolates of HSV in multiple lethal mouse models. To assess durability, we vaccinated mice (2 doses administered intramuscularly) with ΔgD-2, adjuvanted recombinant gD-2 (rgD-2/Alum-MPL), or uninfected cells as a control, and quantified antibody responses over one year. Mice (n = 5/group) were lethally challenged at 2, 4, 6, 8, and 10-months post-boost. ΔgD-2-vaccinated mice elicited a durable ADCC-mediating response, which provided complete protection against challenge at all timepoints. In contrast, rgD-2/Alum-MPL elicited only nAbs, which declined significantly within 6 months, provided only partial protection at early timepoints, and no protection after 6 months. Serum sampling after viral challenge showed that infection elicited low levels of ADCC-mediating antibodies in rgD-2/Alum-MPL-vaccinated mice and boosted the nAb response, but only after 6 months. Conversely, infection significantly and consistently boosted both the ADCC and nAbs responses in ΔgD-2-vaccinated mice. Results recapitulate clinical trial outcomes with gD vaccines, highlight the importance of ADCC, and predict that ΔgD-2 will elicit durable responses in humans.
    Language English
    Publishing date 2023-08-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11081362
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Failure of Herpes Simplex Virus Glycoprotein D Antibodies to Elicit Antibody-Dependent Cell-Mediated Cytotoxicity: Implications for Future Vaccines.

    Mahant, Aakash Mahant / Guerguis, Sandra / Blevins, Tamara P / Cheshenko, Natalia / Gao, Wei / Anastos, Kathryn / Belshe, Robert B / Herold, Betsy C

    The Journal of infectious diseases

    2024  Volume 226, Issue 9, Page(s) 1489–1498

    Abstract: Background: The glycoprotein D (gD)/AS04 vaccine failed to prevent herpes simplex virus (HSV) 2 in clinical trials. Failure was recapitulated in mice, in which the vaccine elicited neutralizing antibody but not antibody-dependent cell-mediated ... ...

    Abstract Background: The glycoprotein D (gD)/AS04 vaccine failed to prevent herpes simplex virus (HSV) 2 in clinical trials. Failure was recapitulated in mice, in which the vaccine elicited neutralizing antibody but not antibody-dependent cell-mediated cytotoxicity (ADCC) responses. Preclinical findings suggest that ADCC is important for protection, but the clinical data are limited. We hypothesized that gD/AS04 and acute HSV-2 infection elicit primarily neutralizing antibodies, whereas ADCC emerges over time.
    Methods: HSV-specific immunoglobulin G, subclass, function (neutralization, C1q binding and ADCC), and antigenic targets were compared (paired t test or Mann-Whitney U test) at enrollment and after gD/AS04 vaccination, before and after HSV-2 acquisition in vaccine controls, and in an independent cohort with chronic HSV-2 infection.
    Results: Vaccination elicited only a neutralizing antibody response, whereas acute infection elicited neutralizing and C1q-binding antibodies but not a significant ADCC response. Antibodies to gD were exclusively immunoglobulin G1 and only neutralizing. In contrast, women with chronic HSV-2 infection had significantly greater ADCC responses and targeted a broader range of viral antigens compared with acutely infected or gD/AS04 vaccine recipients (P < .001).
    Conclusions: Results from gD/AS04 vaccinated or acutely infected women recapitulate murine findings of limited functional antibody responses, supporting the speculation that vaccines that generate polyfunctional and specifically ADCC responses may be required to prevent HSV-2 acquisition and limit recurrences.
    MeSH term(s) Female ; Mice ; Animals ; Complement C1q ; Antibodies, Viral ; Herpesvirus 2, Human ; Herpes Simplex ; Antibodies, Neutralizing ; Antibody-Dependent Cell Cytotoxicity ; Viral Vaccines ; Glycoproteins ; Viral Envelope Proteins ; Herpes Simplex Virus Vaccines
    Chemical Substances Complement C1q (80295-33-6) ; Antibodies, Viral ; Antibodies, Neutralizing ; Viral Vaccines ; Glycoproteins ; Viral Envelope Proteins ; Herpes Simplex Virus Vaccines
    Language English
    Publishing date 2024-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiac284
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Prolonged Preterm Rupture of Membranes Associated with Neonatal Disseminated Herpes Simplex Virus Type 1 at Birth: Is There a Role for Preemptive Test and Treat Strategies in High-Risk Populations?

    Estrada, Fatima / Mahant, Aakash Mahant / Guerguis, Sandra / Sy, Sharlene / Lu, Chuanyong / Reznik, Sandra E / Herold, Betsy C

    Journal of the Pediatric Infectious Diseases Society

    2023  Volume 12, Issue 4, Page(s) 246–247

    MeSH term(s) Infant, Newborn ; Humans ; Pregnancy ; Female ; Herpesvirus 1, Human ; Herpes Simplex/diagnosis ; Herpes Simplex/drug therapy ; Risk Factors ; Pregnancy Complications, Infectious/diagnosis ; Pregnancy Complications, Infectious/drug therapy
    Language English
    Publishing date 2023-04-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2668791-4
    ISSN 2048-7207 ; 2048-7193
    ISSN (online) 2048-7207
    ISSN 2048-7193
    DOI 10.1093/jpids/piac131
    Database MEDical Literature Analysis and Retrieval System OnLINE

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