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  1. Article: Anti-Immune Complex Antibodies are Elicited During Repeated Immunization with HIV Env Immunogens.

    Brown, Sharidan / Antanasijevic, Aleksandar / Sewall, Leigh M / Garcia, Daniel Montiel / Brouwer, Philip J M / Sanders, Rogier W / Ward, Andrew B

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Early antibody responses to easily accessible epitopes on these antigens are directed to non- ... ...

    Abstract Vaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Early antibody responses to easily accessible epitopes on these antigens are directed to non-neutralizing epitopes instead of bnAb epitopes. Autologous neutralizing antibody responses appear upon boosting once immunodominant epitopes are saturated. Here we report another type of antibody response that arises after repeated immunizations with HIV Env immunogens and present the structures of six anti-immune complexes discovered using polyclonal epitope mapping. The anti-immune complex antibodies target idiotopes composed of framework regions of antibodies bound to Env. This work sheds light on current vaccine development efforts for HIV, as well as for other pathogens, in which repeated exposure to antigen is required.
    Language English
    Publishing date 2024-03-17
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.03.15.585257
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of proton therapy on regional [

    Arif, Wejdan M / Elsinga, Philip H / Steenbakkers, Roel J H M / Noordzij, Walter / Barazzuol, Lara / Siang, Kelvin N G Wei / Brouwer, Charlotte L / Giacobbo, Bruno Lima / Dierckx, Rudi A J O / Borra, Ronald J H / Luurtsema, Gert

    Clinical and translational radiation oncology

    2023  Volume 42, Page(s) 100652

    Abstract: Background and purpose: Previous pre-clinical research using [: Materials and methods: Twenty-three head and neck cancer patients treated with IMPT and available [: Results: Three months after IMPT, [: Conclusion: Our findings suggest that 3 ... ...

    Abstract Background and purpose: Previous pre-clinical research using [
    Materials and methods: Twenty-three head and neck cancer patients treated with IMPT and available [
    Results: Three months after IMPT, [
    Conclusion: Our findings suggest that 3 months after completion of IMPT for head and neck cancer, significant increases in the uptake of [
    Language English
    Publishing date 2023-06-19
    Publishing country Ireland
    Document type Journal Article
    ISSN 2405-6308
    ISSN (online) 2405-6308
    DOI 10.1016/j.ctro.2023.100652
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Presentation of HIV-1 envelope glycoprotein trimers on diverse nanoparticle platforms.

    Brouwer, Philip J M / Sanders, Rogier W

    Current opinion in HIV and AIDS

    2019  Volume 14, Issue 4, Page(s) 302–308

    Abstract: Purpose of review: We will discuss recent advances in the development of nanoparticle vaccines presenting HIV-1 envelope trimer vaccines and the immunological mechanisms by which they act.: Recent findings: The multivalent presentation of Env trimers ...

    Abstract Purpose of review: We will discuss recent advances in the development of nanoparticle vaccines presenting HIV-1 envelope trimer vaccines and the immunological mechanisms by which they act.
    Recent findings: The multivalent presentation of Env trimers on nanoparticles is a promising strategy to increase Env immunogenicity. Recent studies have shed light on how Env nanoparticles increase lymph node trafficking and germinal center formation by using the lectin-mediated complement pathway and enhancing the interaction with naïve B cells. Meanwhile, research on different nanoparticle platforms has resulted in improved designs, such as liposomes with improved stability, and the emergence of novel platforms such as protein nanoparticles that self-assemble in vitro. Immmunogenicity studies with these nanoparticles delineate the advantages and expose the limitations of the different nanoparticle platforms.
    Summary: It is becoming increasingly clear that HIV-1 vaccine research might benefit greatly from using nanoparticles presenting Env trimers, particularly during the priming stage of immunization. Among the different nanoparticles that are being pursued, in vitro-assembling nanoparticles allow for greater control of Env quality making them a promising nanoparticle platform.
    MeSH term(s) AIDS Vaccines/administration & dosage ; AIDS Vaccines/chemistry ; AIDS Vaccines/immunology ; Animals ; B-Lymphocytes/immunology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Nanoparticles/administration & dosage ; Nanoparticles/chemistry ; Vaccination ; env Gene Products, Human Immunodeficiency Virus/chemistry ; env Gene Products, Human Immunodeficiency Virus/genetics ; env Gene Products, Human Immunodeficiency Virus/immunology
    Chemical Substances AIDS Vaccines ; env Gene Products, Human Immunodeficiency Virus
    Language English
    Publishing date 2019-04-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2502511-9
    ISSN 1746-6318 ; 1746-630X
    ISSN (online) 1746-6318
    ISSN 1746-630X
    DOI 10.1097/COH.0000000000000549
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Effects up to 20-Year Follow-Up of Preventive Cognitive Therapy in Adults Remitted from Recurrent Depression: The DELTA Study.

    Legemaat, Amanda M / Burger, Huibert / Geurtsen, Gert J / Brouwer, Marlies / Spinhoven, Philip / Denys, Damiaan / Bockting, Claudi L

    Psychotherapy and psychosomatics

    2022  Volume 92, Issue 1, Page(s) 55–64

    Abstract: Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent ... ...

    Abstract Introduction: Major depressive disorder (MDD) is common, and recurrence rates are high. Preventive Cognitive Therapy (PCT), has been shown to prolong time to recurrence and reduce risk of recurrence(s) over 2-10 years in patients with recurrent depression.
    Objective: The aim of the study was to examine the effectiveness of PCT over 20 years on time to first recurrence, cumulative proportion of first recurrences, percentage of depression-free time, mean severity of recurrences, and the number of recurrences within a patient.
    Methods: Adults remitted from recurrent MDD were randomized to PCT or Treatment As Usual (TAU). Clinical outcomes were assessed using the SCID over 20 years. We used Cox regression analyses, Kaplan-Meier analyses, ANOVA, and negative binomial regression and tested for interaction with the number of previous episodes.
    Results: There was a significant interaction effect for number of previous episodes with treatment condition on time to first recurrence (Wald[1, n = 172] = 8.840, p = 0.003). For participants with more than 3 previous episodes, the mean time to recurrence was 4.8 years for PCT versus 1.6 years for TAU; the cumulative proportion of first recurrences was 87.5% for PCT and 100% for TAU. For participants with more than 3 previous episodes, exploratory analyses suggest that PCT had 53% less recurrences and percentage of depression-free time was significantly higher compared to TAU. There were no significant effects on mean severity.
    Conclusions: Up to 20 years, for MDD patients with more than 3 previous episodes, those who received PCT had significantly longer time to a first recurrence and lower recurrence risk and may have less recurrences and more depression-free time compared to TAU. This suggests long term protective effects of PCT up to 20-years.
    MeSH term(s) Humans ; Adult ; Depressive Disorder, Major/prevention & control ; Depressive Disorder, Major/psychology ; Follow-Up Studies ; Cognitive Behavioral Therapy ; Secondary Prevention ; Self Care ; Recurrence ; Chronic Disease ; Treatment Outcome
    Language English
    Publishing date 2022-12-22
    Publishing country Switzerland
    Document type Randomized Controlled Trial ; Journal Article
    ZDB-ID 209490-3
    ISSN 1423-0348 ; 0033-3190
    ISSN (online) 1423-0348
    ISSN 0033-3190
    DOI 10.1159/000527906
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Defining bottlenecks and opportunities for Lassa virus neutralization by structural profiling of vaccine-induced polyclonal antibody responses.

    Brouwer, Philip J M / Perrett, Hailee R / Beaumont, Tim / Nijhuis, Haye / Kruijer, Sabine / Burger, Judith A / Lee, Wen-Hsin / Müller-Kraüter, Helena / Sanders, Rogier W / Strecker, Thomas / van Gils, Marit J / Ward, Andrew B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Lassa fever continues to be a major public health burden in endemic countries in West Africa, yet effective therapies or vaccines are lacking. The isolation of potent and protective neutralizing antibodies against the Lassa virus glycoprotein complex ( ... ...

    Abstract Lassa fever continues to be a major public health burden in endemic countries in West Africa, yet effective therapies or vaccines are lacking. The isolation of potent and protective neutralizing antibodies against the Lassa virus glycoprotein complex (GPC) justifies the development of vaccines that can elicit strong neutralizing antibody responses. However, Lassa vaccines candidates have generally been unsuccessful in doing so and the associated antibody responses to these vaccines remain poorly characterized. Here, we establish an electron-microscopy based epitope mapping pipeline that enables high-resolution structural characterization of polyclonal antibodies to GPC. By applying this method to rabbits vaccinated with a recombinant GPC vaccine and a GPC-derived virus-like particle, we reveal determinants of neutralization which involve epitopes of the GPC-C, GPC-A, and GP1-A competition clusters. Furthermore, by identifying previously undescribed immunogenic off-target epitopes, we expose challenges that recombinant GPC vaccines face. By enabling detailed polyclonal antibody characterization, our work ushers in a next generation of more rational Lassa vaccine design.
    Language English
    Publishing date 2023-12-23
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.12.21.572918
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: A Lassa virus mRNA vaccine confers protection but does not require neutralizing antibody in a guinea pig model of infection.

    Ronk, Adam J / Lloyd, Nicole M / Zhang, Min / Atyeo, Caroline / Perrett, Hailee R / Mire, Chad E / Hastie, Kathryn M / Sanders, Rogier W / Brouwer, Philip J M / Saphire, Erica Olmann / Ward, Andrew B / Ksiazek, Thomas G / Alvarez Moreno, Juan Carlos / Thaker, Harshwardhan M / Alter, Galit / Himansu, Sunny / Carfi, Andrea / Bukreyev, Alexander

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 5603

    Abstract: Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA ... ...

    Abstract Lassa virus is a member of the Arenaviridae family, which causes human infections ranging from asymptomatic to severe hemorrhagic disease with a high case fatality rate. We have designed and generated lipid nanoparticle encapsulated, modified mRNA vaccines that encode for the wild-type Lassa virus strain Josiah glycoprotein complex or the prefusion stabilized conformation of the Lassa virus glycoprotein complex. Hartley guinea pigs were vaccinated with two 10 µg doses, 28 days apart, of either construct. Vaccination induced strong binding antibody responses, specific to the prefusion conformation of glycoprotein complex, which were significantly higher in the prefusion stabilized glycoprotein complex construct group and displayed strong Fc-mediated effects. However, Lassa virus-neutralizing antibody activity was detected in some but not all animals. Following the challenge with a lethal dose of the Lassa virus, all vaccinated animals were protected from death and severe disease. Although the definitive mechanism of protection is still unknown, and assessment of the cell-mediated immune response was not investigated in this study, these data demonstrate the promise of mRNA as a vaccine platform against the Lassa virus and that protection against Lassa virus can be achieved in the absence of virus-neutralizing antibodies.
    MeSH term(s) Humans ; Guinea Pigs ; Animals ; Lassa virus/genetics ; Antibodies, Neutralizing ; Arenaviridae ; mRNA Vaccines ; Glycoproteins
    Chemical Substances Antibodies, Neutralizing ; mRNA Vaccines ; Glycoproteins
    Language English
    Publishing date 2023-09-12
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-41376-6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial.

    Willemsen, Sten P / Knol, Ronny / Brouwer, Emma / van den Akker, Thomas / DeKoninck, Philip L J / Lopriore, Enrico / Onland, Wes / de Boode, Willem P / van Kaam, Anton H / Nuytemans, Debbie H / Reiss, Irwin K M / Hutten, G Jeroen / Prins, Sandra A / Mulder, Estelle E M / Hulzebos, Christian V / van Sambeeck, Sam J / van der Putten, Mayke E / Zonnenberg, Inge A / Te Pas, Arjan B /
    Vermeulen, Marijn J

    Trials

    2024  Volume 25, Issue 1, Page(s) 164

    Abstract: Background: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of ... ...

    Abstract Background: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC.
    Methods: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data.
    Discussion: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth.
    Trial registration: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.
    MeSH term(s) Infant ; Female ; Infant, Newborn ; Humans ; Child, Preschool ; Constriction ; Infant, Premature ; Premature Birth ; Infant, Very Low Birth Weight ; Respiration
    Language English
    Publishing date 2024-03-04
    Publishing country England
    Document type Randomized Controlled Trial ; Multicenter Study ; Journal Article
    ZDB-ID 2040523-6
    ISSN 1745-6215 ; 1468-6694 ; 1745-6215
    ISSN (online) 1745-6215
    ISSN 1468-6694 ; 1745-6215
    DOI 10.1186/s13063-024-08014-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Author Correction: Interplay of diverse adjuvants and nanoparticle presentation of native-like HIV-1 envelope trimers.

    Sliepen, Kwinten / Schermer, Edith / Bontjer, Ilja / Burger, Judith A / Lévai, Réka Felfödiné / Mundsperger, Philipp / Brouwer, Philip J M / Tolazzi, Monica / Farsang, Attila / Katinger, Dietmar / Moore, John P / Scarlatti, Gabriella / Shattock, Robin J / Sattentau, Quentin J / Sanders, Rogier W

    NPJ vaccines

    2021  Volume 6, Issue 1, Page(s) 134

    Language English
    Publishing date 2021-11-02
    Publishing country England
    Document type Published Erratum
    ISSN 2059-0105
    ISSN (online) 2059-0105
    DOI 10.1038/s41541-021-00398-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Importance of complete response for outcomes of pregnancy in patients with autoimmune hepatitis.

    Fischer, Susan E / de Vries, Elsemieke S / Tushuizen, Maarten E / de Boer, Ynto S / van der Meer, Adriaan J P / de Man, Robert A / Brouwer, Johannes T / Kuyvenhoven, Johan P / Klemt-Kropp, Michael / Gevers, Tom J G / Tjwa, Eric T T L / Kuiper, Edith M M / Verhagen, Marc A M T / Friederich, Philip W / van Hoek, Bart

    Liver international : official journal of the International Association for the Study of the Liver

    2023  Volume 43, Issue 4, Page(s) 855–864

    Abstract: Background and aims: While some articles describe outcome of pregnancy in autoimmune hepatitis (AIH), there are less data evaluating influence of AIH control on maternal and perinatal outcomes. This study analysed outcomes of pregnancy and related ... ...

    Abstract Background and aims: While some articles describe outcome of pregnancy in autoimmune hepatitis (AIH), there are less data evaluating influence of AIH control on maternal and perinatal outcomes. This study analysed outcomes of pregnancy and related possible risk factors in AIH.
    Method: A retrospective multicentre cohort study on pregnancy in AIH was performed in 11 hospitals in the Netherlands. Maternal and neonatal outcomes were collected from records and completed by interview. Risk factors-including incomplete response, relapse and cirrhosis-for adverse outcomes were identified using logistic regression analysis.
    Results: Ninety-seven pregnancies in 50 women resulted in 70 deliveries (72%) with a live birth rate of 98.5%. AIH relapse occurred in 6% during pregnancy, and in 27% of post-partum episodes. Absence of complete biochemical response at conception was identified as risk factor for the occurrence of gestational and post-partum relapses. Relapse of AIH in the year before conception was a risk factor for the occurrence of both gestational relapses and post-partum relapses. No complete biochemical response increased the risk for hypertensive disorders during pregnancy and intrahepatic cholestasis of pregnancy (ICP). Cirrhosis was found to be a risk factor for miscarriages, but not for other outcomes.
    Conclusion: Pregnancy in AIH is related to an increased incidence of maternal and fetal/neonatal complications; in most cases, outcome is good. Incomplete biochemical response at conception or relapse in the year before conception are risk factors for gestational and post-partum relapses, for hypertensive disorders and for ICP. Cirrhosis was a risk factor for miscarriages.
    MeSH term(s) Pregnancy ; Infant, Newborn ; Humans ; Female ; Abortion, Spontaneous ; Hypertension, Pregnancy-Induced ; Cohort Studies ; Hepatitis, Autoimmune/complications ; Hepatitis, Autoimmune/epidemiology ; Pregnancy Complications/epidemiology ; Liver Cirrhosis/complications ; Fibrosis ; Pregnancy Outcome ; Retrospective Studies
    Language English
    Publishing date 2023-01-13
    Publishing country United States
    Document type Multicenter Study ; Journal Article
    ZDB-ID 2102783-3
    ISSN 1478-3231 ; 1478-3223
    ISSN (online) 1478-3231
    ISSN 1478-3223
    DOI 10.1111/liv.15511
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  10. Article ; Online: Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.

    Perrett, Hailee R / Brouwer, Philip J M / Hurtado, Jonathan / Newby, Maddy L / Liu, Lin / Müller-Kräuter, Helena / Müller Aguirre, Sarah / Burger, Judith A / Bouhuijs, Joey H / Gibson, Grace / Messmer, Terrence / Schieffelin, John S / Antanasijevic, Aleksandar / Boons, Geert-Jan / Strecker, Thomas / Crispin, Max / Sanders, Rogier W / Briney, Bryan / Ward, Andrew B

    Cell reports

    2023  Volume 42, Issue 5, Page(s) 112524

    Abstract: Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of ... ...

    Abstract Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.
    MeSH term(s) Humans ; Lassa virus ; Antibodies, Neutralizing ; Lassa Fever/prevention & control ; Glycoproteins ; Antigens, Viral
    Chemical Substances Antibodies, Neutralizing ; Glycoproteins ; Antigens, Viral
    Language English
    Publishing date 2023-05-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112524
    Database MEDical Literature Analysis and Retrieval System OnLINE

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