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1. Immunogenicity and reactogenicity of intradermal mRNA-1273 SARS-CoV-2 vaccination: a non-inferiority, randomized-controlled trial

Author

Prins, Manon L. M., Roozen, Geert V. T., Pothast, Cilia. R., Huisman, Wesley, van Binnendijk, Rob, den Hartog, Gerco, Kuiper, Vincent P., Prins, Corine, Janse, Jacqueline J., Lamers, Olivia. A. C., Koopman, Jan Pieter R., Kruithof, Annelieke C., Kamerling, Ingrid M. C., Dijkland, Romy C., de Kroon, Alicia. C., Azimi, Shohreh, Feltkamp, Mariet C. W., Kuijer, Marjan, Jochems, Simon P., Heemskerk, Mirjam H. M., Rosendaal, Frits R., Roestenberg, Meta, Visser, Leo G., and Roukens, Anna H. E.

Published
2024
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8. Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Author

Kant, Iris M.J., Graas, Thecla, Toussaint, Belle, de Jong, Sterre, Darwesh, Shahan, Mahes, Sandjiv S., Kamminga, Dora, Koelewijn, Matthijs, Faber, Gino, Beaumont, Guus, Engel, Marije D., Pierie, R. Cheyenne N., Janssen, Suzanne R., van Dijkman, Edith, Heijmans, Jarom, Witte, Yara Y., Nahui Palomino, Rogers A., Omar, Said Z., Zweegman, Sonja, Kater, Arnon P., van den Vegt, Caya, Arends-Halbesma, Ilonka, de Pater, Emma, Dijkstra, Margriet J., Rots, Nynke Y., Rijnstra, Esther Siteur-van, de Rooij, Dennis M., Sanders, Rogier W., Poniman, Meliawati, Olijhoek, Wouter, van Rijswijk, Jacqueline, Beaumont, Tim, Çetinel, Lusia, Schellekens, Louis, den Hartogh, Yvonne M., Cloos, Jacqueline, Weijers, Suzanne S., Tonouh-Aajoud, Saïda, Avci, Selime, Roelandse-Koop, Elianne, Dik, Willem A., Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Broers, Annoek E.C., van Doesum, Jaap A., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., van Meerloo, Johan, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby P., Wouters, Dorine, van Leeuwen, Ester M.M., Bontkes, Hetty J., Kootstra, Neeltje A., Vogels-Nooijen, Sandra, Rots, Nynke, van Beek, Josine, Heemskerk, Mirjam H.M., Groen, Kazimierz, van Meerten, Tom, Mutsaers, Pim G.N.J., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., and Nijhof, Inger S.

Published
2023
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9. Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1.

Author

den Hartog, Gerco, Butcher, Lindsay D, Ablack, Amber L, Pace, Laura A, Ablack, Jailal NG, Xiong, Richard, Das, Soumita, Stappenbeck, Thaddeus S, Eckmann, Lars, Ernst, Peter B, and Crowe, Sheila E

Subjects
AIEC LF82 strain, Rac1, Salmonella Typhimurium, apurinic/apyrimidinic endonuclease 1, internalization, intestinal epithelial barrier, invasion, apurinic, apyrimidinic endonuclease 1, Immunology, Medical Microbiology
Abstract

Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected with Salmonella enterica serovar Typhimurium or adherent-invasive Escherichia coli. The effects of APE1 inhibition on bacterial internalization, the regulation of Rho GTPase Rac1 as well as the epithelial cell barrier function were assessed. Increased numbers of bacteria were present in APE1-deficient colonic tumor cell lines and primary epithelial cells. Activation of Rac1 was augmented following infection but negatively regulated by APE1. Pharmacological inhibition of Rac1 reversed the increase in intracellular bacteria in APE1-deficient cells whereas overexpression of constitutively active Rac1 augmented the numbers in APE1-competent cells. Enhanced numbers of intracellular bacteria resulted in the loss of barrier function and a delay in its recovery. Our data demonstrate that APE1 inhibits the internalization of invasive bacteria into human intestinal epithelial cells through its ability to negatively regulate Rac1. This activity also protects epithelial cell barrier function.

Published
2020

10. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial

Author

Abrahams, Alferso C., Baas, Marije C., Bouwmans, Pim, ten Dam, Marc A.G.J., Gommers, Lennert, Standaar, Dorien, van der Heiden, Marieke, Adema, Yvonne M.R., Boer-Verschragen, Marieken J., Mattheussens, Wouter B., Philipsen, Ria H.L.A., van Mourik, Djenolan, Bogers, Susanne, van Dijk, Laura L.A., Rots, Nynke, Smits, Gaby, Kuijer, Marjan, Hemmelder, Marc H., Kho, Marcia M L, Messchendorp, A Lianne, Frölke, Sophie C, Imhof, Celine, Koomen, Vera JCH, Malahe, S Reshwan K, Vart, Priya, Geers, Daryl, de Vries, Rory D, GeurtsvanKessel, Corine H, Baan, Carla C, van der Molen, Renate G, Diavatopoulos, Dimitri A, Remmerswaal, Ester B M, van Baarle, Debbie, van Binnendijk, Rob, den Hartog, Gerco, de Vries, Aiko P J, Gansevoort, Ron T, Bemelman, Frederike J, Reinders, Marlies E J, Sanders, Jan-Stephan F, and Hilbrands, Luuk B

Published
2023
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12. SARS‐CoV‐2 Seroprevalence Trends in the Netherlands in the Variant of Concern Era: Input for Future Response

Author

Vos, Eric R. A., primary, van Hagen, Cheyenne C. E., additional, Wong, Denise, additional, Smits, Gaby, additional, Kuijer, Marjan, additional, Wijmenga‐Monsuur, Alienke J., additional, Kaczorowska, Joanna, additional, van Binnendijk, Robert S., additional, van der Klis, Fiona R. M., additional, den Hartog, Gerco, additional, and de Melker, Hester E., additional

Published
2024
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14. SARS-CoV-2 Spike S1-specific IgG kinetic profiles following mRNA or vector-based vaccination in the general Dutch population show distinct kinetics

Author

van den Hoogen, Lotus L., Verheul, Marije K., Vos, Eric R. A., van Hagen, Cheyenne C. E., van Boven, Michiel, Wong, Denise, Wijmenga-Monsuur, Alienke J., Smits, Gaby, Kuijer, Marjan, van Rooijen, Debbie, Bogaard-van Maurik, Marjan, Zutt, Ilse, van Vliet, Jeffrey, Wolf, Janine, van der Klis, Fiona R. M., de Melker, Hester E., van Binnendijk, Robert S., and den Hartog, Gerco

Published
2022
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15. Analysing the protection from respiratory tract infections and allergic diseases early in life by human milk components: the PRIMA birth cohort

Author

van Stigt, Arthur H., Oude Rengerink, Katrien, Bloemenkamp, Kitty W. M., de Waal, Wouter, Prevaes, Sabine M. P. J., Le, Thuy-My, van Wijk, Femke, Nederend, Maaike, Hellinga, Anneke H., Lammers, Christianne S., den Hartog, Gerco, van Herwijnen, Martijn J. C., Garssen, Johan, Knippels, Léon M. J., Verhagen, Lilly M., de Theije, Caroline G. M., Lopez-Rincon, Alejandro, Leusen, Jeanette H. W., van’t Land, Belinda, and Bont, Louis

Published
2022
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16. Quantitative analysis of mRNA-1273 COVID-19 vaccination response in immunocompromised adult hematology patients

Author

Haggenburg, Sabine, Lissenberg-Witte, Birgit I., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., de Rooij, Dennis M., van Meerloo, Johan, Cloos, Jacqueline, Kootstra, Neeltje A., Wouters, Dorine, Weijers, Suzanne S., van Leeuwen, Ester M.M., Bontkes, Hetty J., Tonouh-Aajoud, Saïda, Heemskerk, Mirjam H.M., Sanders, Rogier W., Roelandse-Koop, Elianne, Hofsink, Quincy, Groen, Kazimierz, Çetinel, Lucia, Schellekens, Louis, den Hartog, Yvonne M., Toussaint, Belle, Kant, Iris M.J., Graas, Thecla, de Pater, Emma, Dik, Willem A., Engel, Marije D., Pierie, Cheyenne R.N., Janssen, Suzanne R., van Dijkman, Edith, Poniman, Meliawati, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby, Rots, Nynke Y., Zweegman, Sonja, Kater, Arnon P., van Meerten, Tom, Mutsaers, Pim G.N.J., van Doesum, Jaap A., Broers, Annoek E.C., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., and Nijhof, Inger S.

Published
2022
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17. mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial

Author

Oosting, Sjoukje F, van der Veldt, Astrid A M, GeurtsvanKessel, Corine H, Fehrmann, Rudolf S N, van Binnendijk, Rob S, Dingemans, Anne-Marie C, Smit, Egbert F, Hiltermann, T Jeroen N, den Hartog, Gerco, Jalving, Mathilda, Westphal, Tatjana T, Bhattacharya, Arkajyoti, van der Heiden, Marieke, Rimmelzwaan, Guus F, Kvistborg, Pia, Blank, Christian U, Koopmans, Marion P G, Huckriede, Anke L W, van Els, Cecile A C M, Rots, Nynke Y, van Baarle, Debbie, Haanen, John B A G, and de Vries, Elisabeth G E

Published
2021
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18. Serological profiling of pneumococcal proteins reveals unique patterns of acquisition, maintenance and waning of antibodies throughout life

Author

He, Samantha W J, primary, Voß, Franziska, additional, Nicolaie, Mioara A, additional, Brummelman, Jolanda, additional, van de Garde, Martijn D B, additional, Bijvank, Elske, additional, Poelen, Martien, additional, Wijmenga-Monsuur, Alienke J, additional, Wyllie, Anne L, additional, Trzciński, Krzysztof, additional, Van Beek, Josine, additional, Rots, Nynke Y, additional, den Hartog, Gerco, additional, Hammerschmidt, Sven, additional, and van Els, Cécile A C M, additional

Published
2024
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19. Intradermal delivery of the third dose of the mRNA-1273 SARS-CoV-2 vaccine: safety and immunogenicity of a fractional booster dose

Author

Roozen, Geert V.T., primary, Prins, Manon L.M., additional, Prins, Corine, additional, Janse, Jacqueline J., additional, de Gruyter, Heidi L.M., additional, Pothast, Cilia R., additional, Huisman, Wesley, additional, Koopman, Jan Pieter R., additional, Lamers, Olivia A.C., additional, Kuijer, Marjan, additional, Myeni, Sebenzile K., additional, Binnendijk, Rob S. van, additional, den Hartog, Gerco, additional, Heemskerk, Mirjam H.M., additional, Jochems, Simon P., additional, Feltkamp, Mariet C.W., additional, Kikkert, Marjolein, additional, Rosendaal, Frits R., additional, Roestenberg, Meta, additional, Visser, Leo G., additional, and Roukens, Anna H.E., additional

Published
2024
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21. Oxidative Stress Resulting From Helicobacter pylori Infection Contributes to Gastric Carcinogenesis.

Author

Butcher, Lindsay D, den Hartog, Gerco, Ernst, Peter B, and Crowe, Sheila E

Subjects
AP Endonuclease, APE1, apurinic/apyrimidinic endonuclease 1, BabA, blood group antigen binding adhesion, CagA, cytotoxin-associated gene A, DNA Damage, Gastric Cancer, H pylori, IL, interleukin, NADPH, nicotinamide adenine dinucleotide phosphate, NapA, neutrophil activating factor A, Nox, nicotinamide adenine dinucleotide phosphate oxidase, O2-, superoxide, OH, hydroxyl radical, Oxidative Stress, RNS, reactive nitrogen species, ROS, reactive oxygen species, TGF-β, transforming growth factor β, VacA, vacuolating cytotoxin A, iNOS, inducible nitric oxide synthase, APE1, apurinic/apyrimidinic endonuclease 1, BabA, blood group antigen binding adhesion, CagA, cytotoxin-associated gene A, IL, interleukin, NADPH, nicotinamide adenine dinucleotide phosphate, NapA, neutrophil activating factor A, Nox, nicotinamide adenine dinucleotide phosphate oxidase, O2-, superoxide, OH, hydroxyl radical, RNS, reactive nitrogen species, ROS, reactive oxygen species, TGF-β, transforming growth factor β, VacA, vacuolating cytotoxin A, iNOS, inducible nitric oxide synthase
Abstract

Helicobacter pylori is a gram-negative, microaerophilic bacterium that infects the stomach and can lead to, among other disorders, the development of gastric cancer. The inability of the host to clear the infection results in a chronic inflammatory state with continued oxidative stress within the tissue. Reactive oxygen species and reactive nitrogen species produced by the immune and epithelial cells damage the host cells and can result in DNA damage. H pylori has evolved to evoke this damaging response while blunting the host's efforts to kill the bacteria. This long-lasting state with inflammation and oxidative stress can result in gastric carcinogenesis. Continued efforts to better understand the bacterium and the host response will serve to prevent or provide improved early diagnosis and treatment of gastric cancer.

Published
2017

23. IgG1 glycosylation highlights premature aging in Down syndrome.

Author

Streng, Bianca M. M., Van Coillie, Julie, Wildenbeest, Joanne G., Binnendijk, Rob S., Smits, Gaby, den Hartog, Gerco, Wang, Wenjun, Nouta, Jan, Linty, Federica, Visser, Remco, Wuhrer, Manfred, Vidarsson, Gestur, and Bont, Louis J.

Subjects
PREMATURE aging (Medicine), LIQUID chromatography-mass spectrometry, DOWN syndrome, GLYCOSYLATION, IMMUNE response, FUCOSYLATION
Abstract

Down syndrome (DS) is characterized by lowered immune competence and premature aging. We previously showed decreased antibody response following SARS‐CoV‐2 vaccination in adults with DS. IgG1 Fc glycosylation patterns are known to affect the effector function of IgG and are associated with aging. Here, we compare total and anti‐spike (S) IgG1 glycosylation patterns following SARS‐CoV‐2 vaccination in DS and healthy controls (HC). Total and anti‐Spike IgG1 Fc N‐glycan glycoprofiles were measured in non‐exposed adults with DS and controls before and after SARS‐CoV‐2 vaccination by liquid chromatography–mass spectrometry (LC–MS) of Fc glycopeptides. We recruited N = 44 patients and N = 40 controls. We confirmed IgG glycosylation patterns associated with aging in HC and showed premature aging in DS. In DS, we found decreased galactosylation (50.2% vs. 59.0%) and sialylation (6.7% vs. 8.5%) as well as increased fucosylation (97.0% vs. 94.6%) of total IgG. Both cohorts showed similar bisecting GlcNAc of total and anti‐S IgG1 with age. In contrast, anti‐S IgG1 of DS and HC showed highly comparable glycosylation profiles 28 days post vaccination. The IgG1 glycoprofile in DS exhibits strong premature aging. The combination of an early decrease in IgG1 Fc galactosylation and sialylation and increase in fucosylation is predicted to reduce complement activity and decrease FcγRIII binding and subsequent activation, respectively. The altered glycosylation patterns, combined with decreased antibody concentrations, help us understand the susceptibility to severe infections in DS. The effect of premature aging highlights the need for individuals with DS to receive tailored vaccines and/or vaccination schedules. [ABSTRACT FROM AUTHOR]

Published
2024
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25. The RECOVAC Immune-response Study: The Immunogenicity, Tolerability, and Safety of COVID-19 Vaccination in Patients With Chronic Kidney Disease, on Dialysis, or Living With a Kidney Transplant

Author

Sanders, Jan-Stephan F., Bemelman, Frederike J., Messchendorp, A. Lianne, Baan, Carla C., van Baarle, Debbie, van Binnendijk, Rob, Diavatopoulos, Dimitri A., Frölke, Sophie C., Geers, Daryl, GeurtsvanKessel, Corine H., den Hartog, Gerco, van der Heiden, Marieke, Imhof, Celine, Kho, Marcia M. L., Koopmans, Marion P. G., Malahe, S. Reshwan K., Mattheussens, Wouter B., van der Molen, Renate, van Mourik, Djenolan, Remmerswaal, Ester B. M., Rots, Nynke, Vart, Priya, de Vries, Rory D., Gansevoort, Ron T., Hilbrands, Luuk B., and Reinders, Marlies E. J.

Published
2021
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26. Regulation of Rac1 and Reactive Oxygen Species Production in Response to Infection of Gastrointestinal Epithelia.

Author

den Hartog, Gerco, Chattopadhyay, Ranajoy, Ablack, Amber, Hall, Emily H, Butcher, Lindsay D, Bhattacharyya, Asima, Eckmann, Lars, Harris, Paul R, Das, Soumita, Ernst, Peter B, and Crowe, Sheila E

Subjects
Intestinal Mucosa, Gastric Mucosa, Cell Line, Humans, Salmonella Infections, Helicobacter Infections, Reactive Oxygen Species, DNA-(Apurinic or Apyrimidinic Site) Lyase, rac1 GTP-Binding Protein, Microscopy, Confocal, Fluorescent Antibody Technique, Blotting, Western, Immunoprecipitation, Real-Time Polymerase Chain Reaction, Blotting, Western, Microscopy, Confocal, Virology, Microbiology, Immunology, Medical Microbiology
Abstract

Generation of reactive oxygen species (ROS) during infection is an immediate host defense leading to microbial killing. APE1 is a multifunctional protein induced by ROS and after induction, protects against ROS-mediated DNA damage. Rac1 and NAPDH oxidase (Nox1) are important contributors of ROS generation following infection and associated with gastrointestinal epithelial injury. The purpose of this study was to determine if APE1 regulates the function of Rac1 and Nox1 during oxidative stress. Gastric or colonic epithelial cells (wild-type or with suppressed APE1) were infected with Helicobacter pylori or Salmonella enterica and assessed for Rac1 and NADPH oxidase-dependent superoxide production. Rac1 and APE1 interactions were measured by co-immunoprecipitation, confocal microscopy and proximity ligation assay (PLA) in cell lines or in biopsy specimens. Significantly greater levels of ROS were produced by APE1-deficient human gastric and colonic cell lines and primary gastric epithelial cells compared to control cells after infection with either gastric or enteric pathogens. H. pylori activated Rac1 and Nox1 in all cell types, but activation was higher in APE1 suppressed cells. APE1 overexpression decreased H. pylori-induced ROS generation, Rac1 activation, and Nox1 expression. We determined that the effects of APE1 were mediated through its N-terminal lysine residues interacting with Rac1, leading to inhibition of Nox1 expression and ROS generation. APE1 is a negative regulator of oxidative stress in the gastrointestinal epithelium during bacterial infection by modulating Rac1 and Nox1. Our results implicate APE1 in novel molecular interactions that regulate early stress responses elicited by microbial infections.

Published
2016

28. Nationwide SARS-CoV-2 Seroprevalence Trends in the Netherlands in the Variant of Concern Era, 2021-2022: an Ongoing Prospective Cohort Study

Author

Vos, Eric R.A., primary, van Hagen, Cheyenne C.E., additional, Wong, Denise, additional, Smits, Gaby, additional, Kuijer, Marjan, additional, Wijmenga-Monsuur, Alienke J., additional, Kaczorowska, Joanna, additional, van Binnendijk, Robert S., additional, van der Klis, Fiona R.M., additional, den Hartog, Gerco, additional, and de Melker, Hester E., additional

Published
2023
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30. P1536: SARS-COV-2 INFECTIONS IN PATIENTS WITH HAEMATOLOGIC MALIGNANCIES: EFFECT OF VACCINATION AND THE DEVELOPMENT OF HYBRID IMMUNITY

Author

Haggenburg, Sabine, primary, Reuvekamp, Tom, additional, Hofsink, Quincy, additional, Pothast, Cilia R., additional, Dijkland, Romy C., additional, van Dijk, Kayleigh, additional, Broers, Annoek E.C., additional, van Doesum, Jaap, additional, van Binnendijk, Rob S., additional, den Hartog, Gerco, additional, Bhoekhan, Michel S., additional, Haverkate, Nienke J.E., additional, Vogels-Nooijen, Sandra, additional, Nijhof, Inger S., additional, Heemskerk, Mirjam H.M., additional, Rutten, Caroline E., additional, Goorhuis, Abraham, additional, and Hazenberg, Mette D., additional

Published
2023
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31. Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI): a cohort study

Author

Hofsink, Quincy, primary, Haggenburg, Sabine, additional, Lissenberg-Witte, Birgit I., additional, Broers, Annoek E.C., additional, van Doesum, Jaap A., additional, van Binnendijk, Rob S., additional, den Hartog, Gerco, additional, Bhoekhan, Michel S., additional, Haverkate, Nienke J.E., additional, van Meerloo, Johan, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, Smits, Gaby P., additional, Wouters, Dorine, additional, van Leeuwen, Ester M.M., additional, Bontkes, Hetty J., additional, Kootstra, Neeltje A., additional, Vogels-Nooijen, Sandra, additional, Rots, Nynke, additional, van Beek, Josine, additional, Heemskerk, Mirjam H.M., additional, Groen, Kazimierz, additional, van Meerten, Tom, additional, Mutsaers, Pim G.N.J., additional, van Gils, Marit J., additional, Goorhuis, Abraham, additional, Rutten, Caroline E., additional, Hazenberg, Mette D., additional, Nijhof, Inger S., additional, Kant, Iris M.J., additional, Graas, Thecla, additional, Toussaint, Belle, additional, de Jong, Sterre, additional, Darwesh, Shahan, additional, Mahes, Sandjiv S., additional, Kamminga, Dora, additional, Koelewijn, Matthijs, additional, Faber, Gino, additional, Beaumont, Guus, additional, Engel, Marije D., additional, Pierie, R. Cheyenne N., additional, Janssen, Suzanne R., additional, van Dijkman, Edith, additional, Heijmans, Jarom, additional, Witte, Yara Y., additional, Nahui Palomino, Rogers A., additional, Omar, Said Z., additional, Zweegman, Sonja, additional, Kater, Arnon P., additional, van den Vegt, Caya, additional, Arends-Halbesma, Ilonka, additional, de Pater, Emma, additional, Dijkstra, Margriet J., additional, Rots, Nynke Y., additional, Rijnstra, Esther Siteur-van, additional, de Rooij, Dennis M., additional, Sanders, Rogier W., additional, Poniman, Meliawati, additional, Olijhoek, Wouter, additional, van Rijswijk, Jacqueline, additional, Beaumont, Tim, additional, Çetinel, Lusia, additional, Schellekens, Louis, additional, den Hartogh, Yvonne M., additional, Cloos, Jacqueline, additional, Weijers, Suzanne S., additional, Tonouh-Aajoud, Saïda, additional, Avci, Selime, additional, Roelandse-Koop, Elianne, additional, and Dik, Willem A., additional

Published
2023
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33. Alternative strategies to increase the immunogenicity of COVID-19 vaccines in kidney transplant recipients not responding to two or three doses of an mRNA vaccine (RECOVAC): a randomised clinical trial

Author

Kho, Marcia M L, primary, Messchendorp, A Lianne, additional, Frölke, Sophie C, additional, Imhof, Celine, additional, Koomen, Vera JCH, additional, Malahe, S Reshwan K, additional, Vart, Priya, additional, Geers, Daryl, additional, de Vries, Rory D, additional, GeurtsvanKessel, Corine H, additional, Baan, Carla C, additional, van der Molen, Renate G, additional, Diavatopoulos, Dimitri A, additional, Remmerswaal, Ester B M, additional, van Baarle, Debbie, additional, van Binnendijk, Rob, additional, den Hartog, Gerco, additional, de Vries, Aiko P J, additional, Gansevoort, Ron T, additional, Bemelman, Frederike J, additional, Reinders, Marlies E J, additional, Sanders, Jan-Stephan F, additional, Hilbrands, Luuk B, additional, Abrahams, Alferso C., additional, Baas, Marije C., additional, Bouwmans, Pim, additional, ten Dam, Marc A.G.J., additional, Gommers, Lennert, additional, Standaar, Dorien, additional, van der Heiden, Marieke, additional, Adema, Yvonne M.R., additional, Boer-Verschragen, Marieken J., additional, Mattheussens, Wouter B., additional, Philipsen, Ria H.L.A., additional, van Mourik, Djenolan, additional, Bogers, Susanne, additional, van Dijk, Laura L.A., additional, Rots, Nynke, additional, Smits, Gaby, additional, Kuijer, Marjan, additional, and Hemmelder, Marc H., additional

Published
2023
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35. Fourth mRNA COVID-19 vaccination in immunocompromised patients with haematological malignancies (COBRA KAI):a cohort study

Author

Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Broers, Annoek E.C., van Doesum, Jaap A., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., van Meerloo, Johan, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby P., Wouters, Dorine, van Leeuwen, Ester M.M., Bontkes, Hetty J., Kootstra, Neeltje A., Vogels-Nooijen, Sandra, Rots, Nynke Y., van Beek, Josine, Heemskerk, Mirjam H.M., Groen, Kazimierz, van Meerten, Tom, Mutsaers, Pim G.N.J., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., Nijhof, Inger S., Hofsink, Quincy, Haggenburg, Sabine, Lissenberg-Witte, Birgit I., Broers, Annoek E.C., van Doesum, Jaap A., van Binnendijk, Rob S., den Hartog, Gerco, Bhoekhan, Michel S., Haverkate, Nienke J.E., van Meerloo, Johan, Burger, Judith A., Bouhuijs, Joey H., Smits, Gaby P., Wouters, Dorine, van Leeuwen, Ester M.M., Bontkes, Hetty J., Kootstra, Neeltje A., Vogels-Nooijen, Sandra, Rots, Nynke Y., van Beek, Josine, Heemskerk, Mirjam H.M., Groen, Kazimierz, van Meerten, Tom, Mutsaers, Pim G.N.J., van Gils, Marit J., Goorhuis, Abraham, Rutten, Caroline E., Hazenberg, Mette D., and Nijhof, Inger S.

Abstract

Background: Patients with haematological malignancies have impaired antibody responses to SARS-CoV-2 vaccination. We aimed to investigate whether a fourth mRNA COVID-19 vaccination improved antibody quantity and quality. Methods: In this cohort study, conducted at 5 sites in the Netherlands, we compared antibody concentrations 28 days after 4 mRNA vaccinations (3-dose primary series plus 1 booster vaccination) in SARS-CoV-2 naive, immunocompromised patients with haematological malignancies to those obtained by age-matched, healthy individuals who had received the standard primary 2-dose mRNA vaccination schedule followed by a first booster mRNA vaccination. Prior to and 4 weeks after each vaccination, peripheral blood samples and data on demographic parameters and medical history were collected. Concentrations of antibodies that bind spike 1 (S1) and nucleocapsid (N) protein of SARS-CoV-2 were quantified in binding antibody units (BAU) per mL according to the WHO International Standard for COVID-19 serological tests. Seroconversion was defined as an S1 IgG concentration >10 BAU/mL and a previous SARS-CoV-2 infection as N IgG >14.3 BAU/mL. Antibody neutralising activity was tested using lentiviral-based pseudoviruses expressing spike protein of SARS-CoV-2 wild-type (D614G), Omicron BA.1, and Omicron BA.4/5 variants. This study is registered with EudraCT, number 2021-001072-41. Findings: Between March 24, 2021 and May 4, 2021, 723 patients with haematological diseases were enrolled, of which 414 fulfilled the inclusion criteria for the current analysis. Although S1 IgG concentrations in patients significantly improved after the fourth dose, they remained significantly lower compared to those obtained by 58 age-matched healthy individuals after their first booster (third) vaccination. The rise in neutralising antibody concentration was most prominent in patients with a recovering B cell compartment, although potent responses were also observed in patients with

Published
2023

36. Effects of COVID-19 vaccination and previous infection on Omicron SARS-CoV-2 infection and relation with serology

Author

Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, de Gier, Brechje, Huiberts, Anne J., Hoeve, Christina E., den Hartog, Gerco, van Werkhoven, Henri, van Binnendijk, Rob, Hahné, Susan J.M., de Melker, Hester E., van den Hof, Susan, Knol, Mirjam J., Epi Infectieziekten Team 1, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, de Gier, Brechje, Huiberts, Anne J., Hoeve, Christina E., den Hartog, Gerco, van Werkhoven, Henri, van Binnendijk, Rob, Hahné, Susan J.M., de Melker, Hester E., van den Hof, Susan, and Knol, Mirjam J.

Published
2023

37. Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from July 12, 2021 to June 6, 2022: A prospective cohort study

Author

Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epi Infectieziekten Team 1b, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Huiberts, Anne J, de Gier, Brechje, Hoeve, Christina E, de Melker, Hester E, Hahné, Susan J M, den Hartog, Gerco, Grobbee, Diederick E, van de Wijgert, Janneke H H M, van den Hof, Susan, Knol, Mirjam J, Global Health, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Epi Infectieziekten Team 1b, Infection & Immunity, JC onderzoeksprogramma Infectieziekten, Huiberts, Anne J, de Gier, Brechje, Hoeve, Christina E, de Melker, Hester E, Hahné, Susan J M, den Hartog, Gerco, Grobbee, Diederick E, van de Wijgert, Janneke H H M, van den Hof, Susan, and Knol, Mirjam J

Published
2023

40. Contributors

Author

Akiba, Yasutada, primary, Al Alam, Denise, additional, Al-Sadi, Rana, additional, Aziz, Qasim, additional, Battaglioli, Eric J., additional, Bharucha, Adil E., additional, Blumberg, Richard S., additional, Bohin, Natacha, additional, Bornstein, Joel C., additional, Brierley, Stuart M., additional, Brookes, Simon J.H., additional, Castro, Joel, additional, Chang, Eugene B., additional, Chassaing, Benoit, additional, Cheung, Mary, additional, Ciorba, Matthew A., additional, Crowe, Sheila E., additional, Czerwinski, Michael, additional, Danopoulos, Soula, additional, Das, Soumita, additional, Dempsey, Peter J., additional, den Hartog, Gerco, additional, Enomoto, Hideki, additional, Erickson, Andelain, additional, Ernst, Peter B., additional, Farmer, Adam D., additional, Foong, Jaime P.P., additional, Frey, Mark R., additional, Gewirtz, Andrew T., additional, Ghishan, Fayez K., additional, Gribble, Fiona M., additional, Grundy, Luke, additional, Hao, Marlene M., additional, Harrington, Andrea M., additional, Hennig, Grant W., additional, Hu, Hongzhen, additional, Huizinga, Jan D., additional, Iyer, Shankar S., additional, Kaji, Izumi, additional, Kashyap, Purna C., additional, Kaunitz, Jonathan D., additional, Labus, Jennifer S., additional, Lavoie, Brigitte, additional, Liu, Cambrian Y., additional, Ma, Thomas Y., additional, Ma, Xiaoya, additional, Mawe, Gary M., additional, Merchant, Juanita L., additional, Messer, Jeannette S., additional, Miller, Larry, additional, Naliboff, Bruce D., additional, Nelson, Mark T., additional, Newgreen, Donald F., additional, Nighot, Prashant, additional, Passi, Monica, additional, Polk, D. Brent, additional, Pozo, Maria J., additional, Reimann, Frank, additional, Roberts, Geoffrey P., additional, Roland, Bani C., additional, Ruffle, James K., additional, Said, Hyder, additional, Samuelson, Linda C., additional, Schumacher, Michael A., additional, Shah, Yatrik M., additional, Shea-Donohue, Terez, additional, Shroyer, Noah F., additional, Spence, Jason R., additional, Spencer, Nick J., additional, Spohn, Stephanie N., additional, Stamp, Lincon A., additional, Stenson, William F., additional, Takaki, Miyako, additional, Tillisch, Kirsten, additional, Uesaka, Toshihiro, additional, van den Brink, Gijs R., additional, van Dop, Willemijn A., additional, Vegesna, Anil, additional, von Moltke, Jakob, additional, Wald, Arnold, additional, Westendorp, B. Florien, additional, Whitson, Mathew, additional, Wood, Jackie D., additional, Xu, Hua, additional, Yang, Vincent W., additional, Young, Heather M., additional, Young, Vincent B., additional, Abumrad, Nada A., additional, Alrefai, Waddah A., additional, Ammoury, Rana, additional, Anderson, Gregory J., additional, Asano, Shinji, additional, Bamias, Giorgos, additional, Bhutia, Yangzom D., additional, Blondet, Niviann M., additional, Borel, Patrick, additional, Cifarelli, Vincenza, additional, Collins, James F., additional, Cousins, Robert J., additional, Davidson, Nicholas O., additional, Dawson, Paul A., additional, de Lartigue, Guillaume, additional, Desmarchelier, Charles, additional, Dudeja, Pradeep K., additional, Flores, Shireen R.L., additional, Ganapathy, Vadivel, additional, Ghezzi, Chiara, additional, Gill, Ravinder K., additional, Gorelick, Fred S., additional, Grisham, Matthew B., additional, Harrison, Earl H., additional, Hecht, Gail A., additional, Israel, Dawn A., additional, Jamieson, James D., additional, Katona, Bryson W., additional, Kiela, Pawel R., additional, Kopec, Rachel E., additional, Kowdley, Kris V., additional, LaRusso, Nicholas F., additional, Lee, Seong M., additional, Liddle, Rodger A., additional, Liuzzi, Juan P., additional, Loo, Donald D.F., additional, Lynch, John P., additional, Masyuk, Anatoliy I., additional, Masyuk, Tatyana V., additional, Messner, Donald J., additional, Meyer, Mark B., additional, Murray, Karen F., additional, Nexo, Ebba, additional, Okamoto, Curtis T., additional, Ortega, Bernardo, additional, Pandol, Stephen, additional, Peek, Richard M., additional, Pike, J. Wesley, additional, Priyamvada, Shubha, additional, Proctor, Gordon B., additional, Rajendran, Vazhaikkurichi M., additional, Raybould, Helen E., additional, Rivera-Nieves, Jesus, additional, Said, Hamid M., additional, Sakai, Hideki, additional, Saksena, Seema, additional, Sala-Rabanal, Monica, additional, Schulzke, Jörg-Dieter, additional, Seidler, Ursula E., additional, Shaalan, Abeer K., additional, Sheikh, Irshad A., additional, Thiagarajah, Jay R., additional, Verkman, Alan S., additional, Wang, Xiaoyu, additional, Welling, Paul A., additional, Wolkoff, Allan W., additional, and Wright, Ernest M., additional

Published
2018
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41. Age‐specific severity of severe acute respiratory syndrome coronavirus 2 in February 2020 to June 2021 in the Netherlands.

Author

de Boer, Pieter T., van de Kassteele, Jan, Vos, Eric R. A., van Asten, Liselotte, Dongelmans, Dave A., van Gageldonk‐Lafeber, Arianne B., den Hartog, Gerco, Hofhuis, Agnetha, van der Klis, Fiona, de Lange, Dylan W., Stoeldraijer, Lenny, de Melker, Hester E., Geubbels, Eveline, van den Hof, Susan, and Wallinga, Jacco

Subjects
SARS-CoV-2, COVID-19, BREAKTHROUGH infections
Abstract

Background: The severity of Severe Acute Respiratory Syndrome Coronavirus 2 infection varies with age and time. Here, we quantify how age‐specific risks of hospitalization, intensive care unit (ICU) admission, and death upon infection changed from February 2020 to June 2021 in the Netherlands. Methods: A series of large representative serology surveys allowed us to estimate age‐specific numbers of infections in three epidemic periods (late‐February 2020 to mid‐June 2020, mid‐June 2020 to mid‐February 2021, and mid‐February 2021 to late‐June 2021). We accounted for reinfections and breakthrough infections. Severity measures were obtained by combining infection numbers with age‐specific numbers of hospitalization, ICU admission, and excess all‐cause deaths. Results: There was an accelerating, almost exponential, increase in severity with age in each period. The rate of increase with age was the highest for death and the lowest for hospitalization. In late‐February 2020 to mid‐June 2020, the overall risk of hospitalization upon infection was 1.5% (95% confidence interval [CI] 1.3–1.8%), the risk of ICU admission was 0.36% (95% CI: 0.31–0.42%), and the risk of death was 1.2% (95% CI: 1.0–1.4%). The risk of hospitalization was significantly increased in mid‐June 2020 to mid‐February 2021, while the risk of ICU admission remained stable over time. The risk of death decreased over time, with a significant drop among ≥70‐years‐olds in mid‐February 2021 to late‐June 2021; COVID‐19 vaccination started early January 2021. Conclusion: Whereas the increase in severity of Severe Acute Respiratory Syndrome Coronavirus 2 with age remained stable, the risk of death upon infection decreased over time. A significant drop in risk of death among elderly coincided with the introduction of COVID‐19 vaccination. [ABSTRACT FROM AUTHOR]

Published
2023
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42. A Novel Hypomorphic Apex1 Mouse Model Implicates Apurinic/Apyrimidinic Endonuclease 1 in Oxidative DNA Damage Repair in Gastric Epithelial Cells

Author

Rios-Covian, David, primary, Butcher, Lindsay D., additional, Ablack, Amber L., additional, den Hartog, Gerco, additional, Matsubara, Mason T., additional, Ly, Hong, additional, Oates, Andrew W., additional, Xu, Guorong, additional, Fisch, Kathleen M., additional, Ahrens, Eric T., additional, Toden, Shusuke, additional, Brown, Corrie C., additional, Kim, Kenneth, additional, Le, Dzung, additional, Eckmann, Lars, additional, Dhar, Bithika, additional, Izumi, Tadahide, additional, Ernst, Peter B., additional, and Crowe, Sheila E., additional

Published
2023
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43. Fourth mRNA COVID-19 Vaccination in Immunocompromised Patients with Hematologic Malignancies

Author

Hofsink, Quincy, primary, Haggenburg, Sabine, additional, Lissenberg-Witte, Birgit I., additional, Broers, Annoek E.C., additional, van Doesum, Jaap A., additional, van Binnendijk, Robert Samuel, additional, den Hartog, Gerco, additional, Bhoekhan, Michel S., additional, Haverkate, Nienke J.E., additional, van Meerloo, Johan, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, Smits, Gaby, additional, Wouters, D., additional, van Leeuwen, Ester M.M., additional, Bontkes, Hetty J., additional, Kootstra, Neeltje A., additional, Vogels-Nooijen, Sandra, additional, Rots, Nynke, additional, van Beek, Josine, additional, Heemskerk, Mirjam HM, additional, Groen, Kazimierz, additional, van Meerten, Tom, additional, Mutsaers, Pim G. N. J., additional, van Gils, Marit J., additional, Goorhuis, Abraham, additional, Rutten, Caroline E., additional, Hazenberg, Mette D., additional, Nijhof, Inger S., additional, and Team, COBRA KAI Study, additional

Published
2023
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45. Decreased antibody response after severe acute respiratory syndrome coronavirus 2 vaccination in patients with Down syndrom

Author

Streng, Bianca M M, Bont, Marin, Delemarre, Eveline M, Binnendijk, Rob S, Smit, Gaby, den Hartog, Gerco, Coppus, Antonia M W, de Vries, Esther, Weijerman, Michel E, Lamberts, Regina, de Graaf, Gert, van der Klis, Fiona R, Vidarsson, Gestur, Rave, Neele, Bont, Louis J, Wildenbeest, Joanne G, LS IRAS Tox Algemeen, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, AII - Inflammatory diseases, Landsteiner Laboratory, LS IRAS Tox Algemeen, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, Huisarts & Ziekenhuis, and Tranzo, Scientific center for care and wellbeing

Subjects
Adult, COVID-19 Vaccines, COVID-19 vaccination, SARS-CoV-2, COVID-19/prevention & control, Messenger, Vaccination, COVID-19, antibody response, Antibodies, Viral, Antibodies, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Infectious Diseases, Antibody Formation, Immunology and Allergy, Humans, RNA, RNA, Messenger, Viral, Prospective Studies, Down Syndrome, BNT162 Vaccine
Abstract

The risk of a severe course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults with Down syndrome is increased, resulting in an up to 10-fold increase in mortality, in particular in those >40 years of age. After primary SARS-CoV-2 vaccination, the higher risks remain. In this prospective observational cohort study, SARS-CoV-2 spike S1–specific antibody responses after routine SARS-CoV-2 vaccination (BNT162b2, messenger RNA [mRNA]–1273, or ChAdOx1) in adults with Down syndrome and healthy controls were compared. Adults with Down syndrome showed lower antibody concentrations after 2 mRNA vaccinations or after 2 ChAdOx1 vaccinations. After 2 mRNA vaccinations, lower antibody concentrations were seen with increasing age. Clinical Trials Registration NCT05145348.

Published
2022

46. Safety and Immunogenicity of Intradermal Fractional Dose Administration of the mRNA-1273 Vaccine: A Proof-of-Concept Study

Author

Roozen, Geert V.T., primary, Prins, Margaretha L.M., additional, van Binnendijk, Rob, additional, den Hartog, Gerco, additional, Kuiper, Vincent P., additional, Prins, Corine, additional, Janse, Jacqueline J., additional, Kruithof, Annelieke C., additional, Feltkamp, Mariet C.W., additional, Kuijer, Marjan, additional, Rosendaal, Frits R., additional, Roestenberg, Meta, additional, Visser, Leo G., additional, and Roukens, Anna H.E., additional

Published
2022
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47. Discordant Cellular and Humoral Responses to a 3-Dose COVID-19 mRNA Vaccination Schedule in Patients with Hematologic Malignancies

Author

Pothast, Cilia R., primary, Hofsink, Quincy, additional, Haggenburg, Sabine, additional, Michel, Bhoekhan S., additional, Haverkate, Nienke J.E., additional, Dijkland, Romy C., additional, Van Dijk, Kayleigh, additional, Falkenburg, Frederik J.H., additional, Broers, Annoek E.C., additional, van Doesum, Jaap, additional, Van Binnendijk, Robert S., additional, Den Hartog, Gerco, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, Lissenberg-Witte, Birgit I., additional, Smits, Gaby P., additional, Wouters, Dorine, additional, van Leeuwen, Ester M.M., additional, Bontkes, Hetty J., additional, Kootstra, Neeltje A., additional, Zweegman, Sonja, additional, Kater, Arnon P., additional, Groen, Kaz, additional, van Meerten, Tom, additional, Mutsaers, Pim G.N.J., additional, Beaumont, Tim, additional, Van Gils, Marit J., additional, Goorhuis, Abraham, additional, Hazenberg, Mette D., additional, Nijhof, Inger S., additional, Heemskerk, Mirjam H.M., additional, and Rutten, Caroline E., additional

Published
2022
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48. Sickle Cell Disease Patients Mount Adequate Humoral but Reduced Cellular Responses to COVID-19 Vaccination

Author

Pothast, Cilia R., primary, Hofsink, Quincy, additional, Haggenburg, Sabine, additional, Bhoekhan, Michel, additional, Haverkate, Nienke J.E., additional, Dijkland, Romy C., additional, van Dijk, Kayleigh, additional, Falkenburg, Frederik J.H., additional, Broers, Annoek E.C., additional, van Doesum, Jaap, additional, van Binnendijk, Robert S., additional, den Hartog, Gerco, additional, Burger, Judith A., additional, Bouhuijs, Joey H., additional, Lissenberg-Witte, Birgit I., additional, Smits, Gaby P., additional, Wouters, Dorine, additional, van Leeuwen, Ester M.M., additional, Bontkes, Hetty J., additional, Kootstra, Neeltje A., additional, Zweegman, Sonja, additional, Kater, Arnon P., additional, Groen, Kaz, additional, van Meerten, Tom, additional, Mutsaers, Pim G.N.J., additional, Beaumont, Tim, additional, van Gils, Marit J., additional, Goorhuis, Abraham, additional, Hazenberg, Mette D., additional, Nijhof, Inger S., additional, Heemskerk, Mirjam H.M., additional, and Rutten, Caroline E., additional

Published
2022
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49. Reduced Antibody Acquisition with Increasing Age following Vaccination with BNT162b2: Results from Two Longitudinal Cohort Studies in The Netherlands

Author

van den Hoogen, Lotus Leonie, primary, Boer, Mardi, additional, Postema, Abigail, additional, de Rond, Lia, additional, de Zeeuw-Brouwer, Mary-lène, additional, Pronk, Inge, additional, Wijmenga-Monsuur, Alienke Jentien, additional, Bijvank, Elske, additional, Kruiper, Caitlyn, additional, Beckers, Lisa, additional, Maurik, Marjan Bogaard-van, additional, Zutt, Ilse, additional, van Vliet, Jeffrey, additional, van Bergen, Rianne, additional, Kuijer, Marjan, additional, Smits, Gaby, additional, Verschuren, W. M. Monique, additional, Picavet, H. Susan J., additional, van der Klis, Fiona Regina Maria, additional, den Hartog, Gerco, additional, van Binnendijk, Robert Samuel, additional, and Buisman, Anne-Marie, additional

Published
2022
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50. Decreased antibody response after SARS-CoV-2 vaccination in patients with Down Syndrome

Author

Streng, Bianca M M, Bont, Marin, Delemarre, Eveline M, Binnendijk, Rob S, Smit, Gaby, den Hartog, Gerco, Coppus, Antonia M W, de Vries, Esther, Weijerman, Michel E, Lamberts, Regina, de Graaf, Gert, van der Klis, Fiona R, Vidarsson, Gestur, Rave, Neele, Bont, Louis J, and Wildenbeest, Joanne G

Subjects
COVID-19 vaccination, SARS-CoV, Down syndrome, Antibody response
Published
2022

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