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  1. Article: Challenges for the Newborn Immune Response to Respiratory Virus Infection and Vaccination.

    Crofts, Kali F / Alexander-Miller, Martha A

    Vaccines

    2020  Volume 8, Issue 4

    Abstract: The initial months of life reflect an extremely challenging time for newborns as a naïve immune system is bombarded with a large array of pathogens, commensals, and other foreign entities. In many instances, the immune response of young infants is ... ...

    Abstract The initial months of life reflect an extremely challenging time for newborns as a naïve immune system is bombarded with a large array of pathogens, commensals, and other foreign entities. In many instances, the immune response of young infants is dampened or altered, resulting in increased susceptibility and disease following infection. This is the result of both qualitative and quantitative changes in the response of multiple cell types across the immune system. Here we provide a review of the challenges associated with the newborn response to respiratory viral pathogens as well as the hurdles and advances for vaccine-mediated protection.
    Language English
    Publishing date 2020-09-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines8040558
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Analysis of R848 as an Adjuvant to Improve Inactivated Influenza Vaccine Immunogenicity in Elderly Nonhuman Primates.

    Crofts, Kali F / Holbrook, Beth C / D'Agostino, Ralph B / Alexander-Miller, Martha A

    Vaccines

    2022  Volume 10, Issue 4

    Abstract: Elderly individuals are highly susceptible to developing severe outcomes as a result of influenza A virus (IAV) infection. This can be attributed to alterations that span the aged immune system, which also result in reduced responsiveness to the seasonal ...

    Abstract Elderly individuals are highly susceptible to developing severe outcomes as a result of influenza A virus (IAV) infection. This can be attributed to alterations that span the aged immune system, which also result in reduced responsiveness to the seasonal inactivated vaccine. Given the rapidly increasing number of individuals in this age group, it is imperative that we develop strategies that can better protect this population from IAV-associated disease. Based on our previous findings that the TLR7/8 agonist resiquimod (R848) could efficiently boost responses in the newborn, another population with decreased vaccine responsiveness, we evaluated this adjuvant in an elderly African green monkey (AGM) model. AGM aged 16-24 years old (equivalent to 64-96 in human years) were primed and boosted with inactivated A/PuertoRico/8/1934 (H1N1) (IPR8) alone or directly linked to R848 (IPR8-R848). We observed increases in the level of circulating virus-specific IgM antibody 10 days following primary vaccination in AGM that were vaccinated with IPR8-R848, but not IPR8 alone. In addition, there were significant increases in virus-specific IgG after boosting selectively in the IPR8-R848 vaccinated animals. These findings provide insights into the ability of R848 to modulate the aged immune system in the context of IAV vaccination.
    Language English
    Publishing date 2022-03-23
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10040494
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Neuraminidase-specific antibody responses are generated in naive and vaccinated newborn nonhuman primates following virus infection.

    Shultz, Patrick K / Crofts, Kali F / Holbrook, Beth C / Alexander-Miller, Martha A

    JCI insight

    2020  Volume 5, Issue 24

    Abstract: Individuals younger than 6 months of age are at significant risk from influenza virus infection; however, there is currently no vaccine approved for this age group. Influenza virus neuraminidase (NA) has emerged as a potential additional target for ... ...

    Abstract Individuals younger than 6 months of age are at significant risk from influenza virus infection; however, there is currently no vaccine approved for this age group. Influenza virus neuraminidase (NA) has emerged as a potential additional target for vaccine strategies. In this study, we sought to understand the ability of newborns to mount an antibody response to NA. Here we employed a nonhuman primate model, given the similarities to humans in immune system and development. We measured antibody to NA following infection with an H1N1 virus or following vaccination and challenge. Administration of an inactivated virus vaccine was not capable of eliciting detectable NA-specific antibody, even in the presence of adjuvants previously shown to increase total virus-specific IgG. However, both naive and vaccinated newborns generated a NA-specific antibody response following virus infection. Interestingly, the presence of the vaccine-induced response did not prevent generation of systemic antibody to NA following challenge, although the respiratory response was reduced in a significant portion of newborns. These findings are the first, to our knowledge, to evaluate the newborn response to the influenza NA protein as well as the impact of previous vaccination on generation of these antibodies following virus infection.
    MeSH term(s) Adjuvants, Immunologic/administration & dosage ; Animals ; Animals, Newborn/immunology ; Antibodies, Viral/immunology ; Antibody Formation/immunology ; Chlorocebus aethiops/immunology ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines/immunology ; Influenza Vaccines/pharmacology ; Neuraminidase/immunology ; Orthomyxoviridae Infections/immunology ; Primates/immunology ; Vaccination ; Vaccines, Inactivated/immunology
    Chemical Substances Adjuvants, Immunologic ; Antibodies, Viral ; Influenza Vaccines ; Vaccines, Inactivated ; Neuraminidase (EC 3.2.1.18)
    Language English
    Publishing date 2020-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.141655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: An Analysis of Linker-Dependent Effects on the APC Activation and In Vivo Immunogenicity of an R848-Conjugated Influenza Vaccine.

    Crofts, Kali F / Page, Courtney L / Swedik, Stephanie M / Holbrook, Beth C / Meyers, Allison K / Zhu, Xuewei / Parsonage, Derek / Westcott, Marlena M / Alexander-Miller, Martha A

    Vaccines

    2023  Volume 11, Issue 7

    Abstract: Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters ... ...

    Abstract Subunit or inactivated vaccines comprise the majority of vaccines used against viral and bacterial pathogens. However, compared to their live/attenuated counterparts, these vaccines often demonstrate reduced immunogenicity, requiring multiple boosters and or adjuvants to elicit protective immune responses. For this reason, studies of adjuvants and the mechanism through which they can improve inactivated vaccine responses are critical for the development of vaccines with increased efficacy. Studies have shown that the direct conjugation of adjuvant to antigen promotes vaccine immunogenicity, with the advantage of both the adjuvant and antigen targeting the same cell. Using this strategy of direct linkage, we developed an inactivated influenza A (IAV) vaccine that is directly conjugated with the Toll-like receptor 7/8 agonist resiquimod (R848) through a heterobifunctional crosslinker. Previously, we showed that this vaccine resulted in improved protection and viral clearance in newborn nonhuman primates compared to a non-adjuvanted vaccine. We subsequently discovered that the choice of linker used to conjugate R848 to the virus alters the stimulatory activity of the vaccine, promoting increased maturation and proinflammatory cytokine production from DC differentiated in vitro. With this knowledge, we explored how the choice of crosslinker impacts the stimulatory activity of these vaccines. We found that the linker choice alters signaling through the NF-κB pathway in human monocyte-derived dendritic cells (moDCs). Further, we extended our analyses to in vivo differentiated APC present in human peripheral blood, replicating the linker-dependent differences found in in vitro differentiated cells. Finally, we demonstrated in a mouse model that the choice of linker impacts the amount of IAV-specific IgG antibody produced in response to vaccination. These data enhance our understanding of conjugation approaches for improving vaccine immunogenicity.
    Language English
    Publishing date 2023-07-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines11071261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: TCR Dependent Metabolic Programming Regulates Autocrine IL-4 Production Resulting in Self-Tuning of the CD8

    Crofts, Kali F / Holbrook, Beth C / Soto-Pantoja, David R / Ornelles, David A / Alexander-Miller, Martha A

    Frontiers in immunology

    2020  Volume 11, Page(s) 540

    Abstract: The ability of T cells to sense and respond to environmental cues by altering their functional capabilities is critical for a safe and optimally protective immune response. One of the important properties that contributes to this goal is the activation ... ...

    Abstract The ability of T cells to sense and respond to environmental cues by altering their functional capabilities is critical for a safe and optimally protective immune response. One of the important properties that contributes to this goal is the activation set-point of the T cell. Here we report a new pathway through which TCR transgenic OT-I CD8
    MeSH term(s) Animals ; Autocrine Communication/immunology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Interleukin-4/biosynthesis ; Lymphocyte Activation/immunology ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell/immunology
    Chemical Substances Receptors, Antigen, T-Cell ; Interleukin-4 (207137-56-2)
    Language English
    Publishing date 2020-03-31
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.00540
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Viral immunity: Basic mechanisms and therapeutic applications-a Keystone Symposia report.

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L / McGargill, Maureen A / Weiskopf, Daniela / Mettelman, Robert C / Niessl, Julia / Thomas, Paul G / Briney, Bryan / Valkenburg, Sophie A / Bloom, Jesse D / Bjorkman, Pamela J / Iketani, Sho /
    Rappazzo, C Garrett / Crooks, Chelsea M / Crofts, Kali F / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J / Nabel, Gary J / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    MeSH term(s) Humans ; Pandemics ; Influenza, Human/epidemiology
    Language English
    Publishing date 2023-01-30
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Viral immunity

    Cable, Jennifer / Balachandran, Siddharth / Daley-Bauer, Lisa P. / Rustagi, Arjun / Antony, Ferrin / Frere, Justin J. / Strampe, Jamie / Kedzierska, Katherine / Cannon, Judy L. / McGargill, Maureen A. / Weiskopf, Daniela / Mettelman, Robert C. / Niessl, Julia / Thomas, Paul G. / Briney, Bryan / Valkenburg, Sophie A. / Bloom, Jesse D. / Bjorkman, Pamela J. / Iketani, Sho /
    Rappazzo, C. Garrett / Crooks, Chelsea M. / Crofts, Kali F. / Pöhlmann, Stefan / Krammer, Florian / Sant, Andrea J. / Nabel, Gary J. / Schultz-Cherry, Stacey

    Annals of the New York Academy of Sciences

    Basic mechanisms and therapeutic applications - A Keystone Symposia report

    2023  Volume 1521, Issue 1, Page(s) 32–45

    Abstract: Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses ... ...

    Title translation Virale Immunität: Grundlegende Mechanismen und therapeutische Anwendungen - Ein Bericht des Keystone-Symposiums
    Abstract Viruses infect millions of people each year. Both endemic viruses circulating throughout the population as well as novel epidemic and pandemic viruses pose ongoing threats to global public health. Developing more effective tools to address viruses requires not only in-depth knowledge of the virus itself but also of our immune system's response to infection. On June 29 to July 2, 2022, researchers met for the Keystone symposium "Viral Immunity: Basic Mechanisms and Therapeutic Applications." This report presents concise summaries from several of the symposium presenters.
    Keywords Antibodies ; Antikörper ; COVID-19 ; Drohung ; Epidemics ; Epidemien ; Immune System ; Immunity (Disease) ; Immunität (Krankheit) ; Immunsystem ; Infectious Disorders ; Infektionskrankheiten ; Pandemics ; Pandemie ; Public Health ; Threat ; Viral Infections ; Viruserkrankungen ; Öffentliche Gesundheit
    Language English
    Document type Article
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/nyas.14960
    Database PSYNDEX

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    In stock of ZB MED Cologne/Königswinter

    Se 110: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
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