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Article ; Online: Letter to the Editor.

Bakker, Jaco / Remarque, Ed / Kramer, Robin

Journal of the American Association for Laboratory Animal Science : JAALAS

2022 Volume 61, Issue 4, Page(s) 313–314

Language	English
Publishing date	2022-07-12
Publishing country	United States
Document type	Letter ; Comment
ISSN	2769-6677
ISSN (online)	2769-6677
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Article: The nearest neighbor nuclei method to objectify analysis of pertussis toxin-induced clustering.

Hoonakker, Marieke E / Remarque, Ed / Veth, Jennifer / Sloots, Arjen / Bajramovic, Jeffrey J

ALTEX

2021 Volume 39, Issue 1, Page(s) 140–148

Abstract: The in vivo histamine sensitization test (HIST) has historically been performed to guarantee the safety of acellular pertussis vaccine batches. Non-compliance of batches is primarily associated with the presence of low levels of pertussis toxin (PTx). ... ...

Abstract	The in vivo histamine sensitization test (HIST) has historically been performed to guarantee the safety of acellular pertussis vaccine batches. Non-compliance of batches is primarily associated with the presence of low levels of pertussis toxin (PTx). Because of ethical, standardization and scientific reasons, a variety of alternative in vitro approaches have been studied to replace the lethal HIST. A broadly applied and partially accepted method is the CHO cell clustering test, which is based on the clustered growth pattern of CHO cells when exposed to minute amounts of PTx. One of the major hurdles for global application of the CHO clustering test is the manual assessment of the clusters, which is associated with suboptimal reproducibility of test outcomes and is time-consuming. Here, various parameters of CHO cell nuclei were evaluated in search for a reliable, objective read-out parameter. We demonstrate that the distance between each nucleus and its nearest neighbor (3N method) is the most suitable parameter to assess clustered cell growth. This method detects 2.8 mIU PTx/mL and thereby complies with the requirement set for the sensitivity of the CHO clustering test based on visual reading. In commercial acellular pertussis vaccines spiked with PTx, the method detects 45 mIU/mL PTx, which is substantially lower than the 181-725 mIU/mL PTx detected by visual interpretation. The 3N method thus allows objective and sensitive assessment of CHO clustering and thereby encourages broad and global implementation of the in vitro test as an alternative to the HIST.
MeSH term(s)	Animal Testing Alternatives ; Animals ; Cell Nucleus ; Cluster Analysis ; Cricetinae ; Cricetulus ; Pertussis Toxin ; Reproducibility of Results ; Vaccines, Acellular
Chemical Substances	Vaccines, Acellular ; Pertussis Toxin (EC 2.4.2.31)
Language	English
Publishing date	2021-10-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	165707-0
ISSN	1868-596X ; 1018-4562 ; 0946-7785
ISSN	1868-596X ; 1018-4562 ; 0946-7785
DOI	10.14573/altex.2012171
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Article ; Online: Acceleration of Amyloidosis by Inflammation in the Amyloid-Beta Marmoset Monkey Model of Alzheimer's Disease.

Philippens, Ingrid H / Ormel, Paul R / Baarends, Guus / Johansson, Maja / Remarque, Ed J / Doverskog, Magnus

Journal of Alzheimer's disease : JAD

2017 Volume 55, Issue 1, Page(s) 101–113

Abstract: Background: The immune system is increasingly mentioned as a potential target for Alzheimer's disease (AD) treatment.: Objective: In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, ... ...

Abstract	Background: The immune system is increasingly mentioned as a potential target for Alzheimer's disease (AD) treatment. Objective: In the present pilot study, the effect of (neuro)inflammation on amyloidopathy was investigated in the marmoset monkey, which has potential as an AD animal model due to its natural cerebral amyloidosis similar to humans. Methods: Six adult/aged marmosets (Callithrix jacchus) were intracranial injected with amyloid-beta (Aβ) fibrils at three cortical locations in the right hemisphere. Additionally, in half of the monkeys, lipopolysaccharide (LPS) was co-injected with the Aβ fibrils and injected in the other hemisphere without Aβ fibrils. The other three monkeys received phosphate buffered saline instead of LPS, as a control for the inflammatory state. The effect of inflammation on amyloidopathy was also investigated in an additional monkey that suffered from chronic inflammatory wasting syndrome. Mirror histology sections were analyzed to assess amyloidopathy and immune reaction, and peripheral blood for AD biomarker expression. Results: All LPS-injected monkeys showed an early AD immune blood cell expression profile on CD95 and CD45RA. Two out of three monkeys injected with Aβ and LPS and the additional monkey, suffering from chronic inflammation, developed plaques. None of the controls, injected with Aβ only, developed any plaques. Conclusion: This study shows the importance of immune modulation on the susceptibility for amyloidosis, a hallmark of AD, which offers new perspectives for disease modifying approaches in AD.
Language	English
Publishing date	2017
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1440127-7
ISSN	1875-8908 ; 1387-2877
ISSN (online)	1875-8908
ISSN	1387-2877
DOI	10.3233/JAD-160673
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Article ; Online: 25-OH-vitamin D, parathyroid hormone, and calcium serum levels in captive common marmosets (Callithrix jacchus): Reference values and effect of age, sex, season, and closure of long bone epiphyses.

Bosseler, Leslie / Bakker, Jaco / Duchateau, Luc / Remarque, Ed / Langermans, Jan A M / Cornillie, Pieter / Chiers, Koen

Journal of medical primatology

2018 Volume 47, Issue 3, Page(s) 172–177

Abstract: Background: To date, reference values for 25-OH-vitamin D, parathyroid hormone (PTH), and calcium in serum of common marmosets (Callithrix jacchus) based on a large sample size are not available.: Methods: Serum reference values for these parameters ... ...

Abstract	Background: To date, reference values for 25-OH-vitamin D, parathyroid hormone (PTH), and calcium in serum of common marmosets (Callithrix jacchus) based on a large sample size are not available. Methods: Serum reference values for these parameters were determined and correlated with sex, age, season of sampling, and time of long bone epiphyseal closure in captive-housed marmosets. Results and conclusions: The 90% reference range for serum 25-OH-vitamin D is 47.40-370.4 nmol/L, for PTH 2.10-30.51 pmol/L, and for calcium 2.08-2.63 mmol/L. Lower levels of vitamin D were measured in fall compared with the other seasons. Levels of PTH were higher in males than in females, and calcium levels were lower in younger animals compared with older marmosets. No other effects of age, sex, season, or timing of growth plate closure were found.
MeSH term(s)	Age Factors ; Animals ; Calcium/blood ; Callithrix/metabolism ; Epiphyses/growth & development ; Female ; Growth Plate/growth & development ; Male ; Parathyroid Hormone/blood ; Reference Values ; Seasons ; Sex Factors ; Vitamin D/blood
Chemical Substances	Parathyroid Hormone ; Vitamin D (1406-16-2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2018-02-15
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	121206-0
ISSN	1600-0684 ; 0047-2565
ISSN (online)	1600-0684
ISSN	0047-2565
DOI	10.1111/jmp.12334
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Article ; Online: Placental Malaria is Associated with Higher LILRB2 Expression in Monocyte Subsets and Lower Anti-Malarial IgG Antibodies During Infancy.

Frontiers in immunology

2022 Volume 13, Page(s) 909831

Abstract: Background: Placental malaria (PM) is associated with a higher susceptibility of infants to : Method: Infants of women with or without PM were enrolled in Allada, southern Benin, and followed-up for 24 months. Antibodies with specificity for five ... ...

Abstract	Background: Placental malaria (PM) is associated with a higher susceptibility of infants to Method: Infants of women with or without PM were enrolled in Allada, southern Benin, and followed-up for 24 months. Antibodies with specificity for five blood stage parasite antigens were quantified by ELISA, and the frequency of immune cell subsets was quantified by flow cytometry. LILRB1 or LILRB2 expression was assessed on cells collected at 18 and 24 months of age. Findings: Infants born to women with PM had a higher risk of developing symptomatic malaria than those born to women without PM (IRR=1.53, p=0.040), and such infants displayed a lower frequency of non-classical monocytes (OR=0.74, p=0.01) that overexpressed LILRB2 (OR=1.36, p=0.002). Moreover, infants born to women with PM had lower levels of cytophilic IgG and higher levels of IL-10 during active infection. Interpretation: Modulation of IgG and IL-10 levels could impair monocyte functions (opsonisation/phagocytosis) in infants born to women with PM, possibly contributing to their higher susceptibility to malaria. The long-lasting effect of PM on infants' monocytes was notable, raising questions about the capacity of ligands such as Rifins or HLA-I molecules to bind to LILRB1 and LILRB2 and to modulate immune responses, and about the reprogramming of neonatal monocytes/macrophages.
MeSH term(s)	Antibodies, Protozoan ; Antimalarials ; Female ; Humans ; Immunoglobulin G/blood ; Infant ; Infant, Newborn ; Interleukin-10 ; Leukocyte Immunoglobulin-like Receptor B1/genetics ; Leukocyte Immunoglobulin-like Receptor B1/immunology ; Malaria, Falciparum ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Monocytes/metabolism ; Placenta/parasitology ; Plasmodium falciparum ; Pregnancy ; Receptors, Immunologic/genetics ; Receptors, Immunologic/immunology
Chemical Substances	Antibodies, Protozoan ; Antimalarials ; Immunoglobulin G ; LILRB2 protein, human ; Leukocyte Immunoglobulin-like Receptor B1 ; Membrane Glycoproteins ; Receptors, Immunologic ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2022-07-12
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.909831
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Article ; Online: Down selecting adjuvanted vaccine formulations: a comparative method for harmonized evaluation.

Younis, Sumera Y / Barnier-Quer, Christophe / Heuking, Simon / Sommandas, Vinod / Brunner, Livia / Vd Werff, Nicole / Dubois, Patrice / Friede, Martin / Kocken, Clemens / Collin, Nicolas / Remarque, Ed

BMC immunology

2018 Volume 19, Issue 1, Page(s) 6

Abstract: Background: The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine ... ...

Abstract	Background: The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a harmonized fashion. Three reference antigens: Plasmodium falciparum apical membrane antigen 1 (AMA1), hepatitis B virus surface antigen (HBsAg), and Mycobacterium tuberculosis antigen 85A (Ag85A), were selected as model antigens and were each formulated with three adjuvants: aluminium oxyhydroxide, squalene-in-water emulsion, and a liposome formulation mixed with the purified saponin fraction QS21. Results: The nine antigen/adjuvant formulations were assessed for stability and immunogenicity in mice in order to provide benchmarks against which other formulations could be compared, in order to assist subsequent down selection of adjuvanted vaccines. Furthermore, mouse cellular immune responses were analyzed by measuring IFN-γ and IL-5 production in splenocytes by ELISPOT, and humoral responses were determined by antigen-specific ELISA, where levels of total IgG, IgG1, IgG2b and IgG2c in serum samples were determined. Conclusions: The reference antigens and adjuvants described in this study, which span a spectrum of immune responses, are of potential use as tools to act as points of reference in vaccine development studies. The harmonized methodology described herein may be used as a tool for adjuvant/antigen comparison studies.
MeSH term(s)	Acyltransferases/immunology ; Adjuvants, Immunologic/analysis ; Animals ; Antigens, Bacterial/immunology ; Antigens, Protozoan/immunology ; Enzyme-Linked Immunosorbent Assay/methods ; Enzyme-Linked Immunospot Assay/methods ; Hepatitis B Surface Antigens/immunology ; Immunization ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Interferon-gamma/immunology ; Interferon-gamma/metabolism ; Interleukin-5/immunology ; Interleukin-5/metabolism ; Membrane Proteins/immunology ; Mice, Inbred C57BL ; Protozoan Proteins/immunology ; Reproducibility of Results ; Spleen/cytology ; Spleen/immunology ; Spleen/metabolism ; Vaccines/analysis ; Vaccines/immunology
Chemical Substances	Adjuvants, Immunologic ; Antigens, Bacterial ; Antigens, Protozoan ; Hepatitis B Surface Antigens ; Immunoglobulin G ; Interleukin-5 ; Membrane Proteins ; Protozoan Proteins ; Vaccines ; apical membrane antigen I, Plasmodium ; Interferon-gamma (82115-62-6) ; Acyltransferases (EC 2.3.-) ; antigen 85A, Mycobacterium tuberculosis (EC 2.3.1.-)
Language	English
Publishing date	2018-01-31
Publishing country	England
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041500-X
ISSN	1471-2172 ; 1471-2172
ISSN (online)	1471-2172
ISSN	1471-2172
DOI	10.1186/s12865-018-0245-0
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Article: The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues

Böszörményi, Kinga P. / Stammes, Marieke A. / Fagrouch, Zahra C. / Kiemenyi-Kayere, Gwendoline / Niphuis, Henk / Mortier, Daniella / van Driel, Nikki / Nieuwenhuis, Ivonne / Vervenne, Richard A. W. / Haaksma, Tom / Ouwerling, Boudewijn / Adema, Deborah / Acar, Roja Fidel / Zuiderwijk-Sick, Ella / Meijer, Lisette / Mooij, Petra / Remarque, Ed J. / Oostermeijer, Herman / Koopman, Gerrit /

Hoste, Alexis C. R. / Sastre, Patricia / Haagmans, Bart L. / Bontrop, Ronald E. / Langermans, Jan A. M. / Bogers, Willy M. / Kondova, Ivanela / Verschoor, Ernst J. / Verstrepen, Babs E.

Viruses. 2021 Aug. 23, v. 13, no. 8

2021

Abstract: The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally ... ...

Abstract	The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis). During the acute phase of infection, SARS-CoV-2 was shed via the nose and throat, and viral RNA was occasionally detected in feces. This phase coincided with a transient change in systemic immune activation. Even after the alleged resolution of the infection, computed tomography (CT) and positron emission tomography (PET)-CT revealed pulmonary lesions and activated tracheobronchial lymph nodes in all animals. Post-mortem histological examination of the lung tissue revealed mostly marginal or resolving minimal lesions that were indicative of SARS-CoV-2 infection. Evidence for SARS-CoV-2-induced histopathology was also found in extrapulmonary tissue samples, such as conjunctiva, cervical, and mesenteric lymph nodes. However, 5–6 weeks after SARS-CoV-2 exposure, upon necropsy, viral RNA was still detectable in a wide range of tissue samples in 50% of the macaques and included amongst others the heart, the respiratory tract and surrounding lymph nodes, salivary gland, and conjunctiva. Subgenomic messenger RNA was detected in the lungs and tracheobronchial lymph nodes, indicative of ongoing virus replication during the post-acute phase. These results could be relevant for understanding the long-term consequences of COVID-19 in humans.
Keywords	COVID-19 infection ; Macaca fascicularis ; Macaca mulatta ; Severe acute respiratory syndrome coronavirus 2 ; conjunctiva ; feces ; heart ; histology ; histopathology ; lungs ; lymph ; messenger RNA ; necropsy ; nose ; positron-emission tomography ; salivary glands ; throat ; virus replication
Language	English
Dates of publication	2021-0823
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081673
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: The Post-Acute Phase of SARS-CoV-2 Infection in Two Macaque Species Is Associated with Signs of Ongoing Virus Replication and Pathology in Pulmonary and Extrapulmonary Tissues.

Böszörményi, Kinga P / Stammes, Marieke A / Fagrouch, Zahra C / Kiemenyi-Kayere, Gwendoline / Niphuis, Henk / Mortier, Daniella / van Driel, Nikki / Nieuwenhuis, Ivonne / Vervenne, Richard A W / Haaksma, Tom / Ouwerling, Boudewijn / Adema, Deborah / Acar, Roja Fidel / Zuiderwijk-Sick, Ella / Meijer, Lisette / Mooij, Petra / Remarque, Ed J / Oostermeijer, Herman / Koopman, Gerrit /

Hoste, Alexis C R / Sastre, Patricia / Haagmans, Bart L / Bontrop, Ronald E / Langermans, Jan A M / Bogers, Willy M / Kondova, Ivanela / Verschoor, Ernst J / Verstrepen, Babs E

Viruses

2021 Volume 13, Issue 8

Abstract: The post-acute phase of SARS-CoV-2 infection was investigated in rhesus ( ...

Abstract	The post-acute phase of SARS-CoV-2 infection was investigated in rhesus (
MeSH term(s)	Animals ; Antibodies, Viral/blood ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/virology ; Cytokines/blood ; Disease Models, Animal ; Humans ; Lung/pathology ; Lung/virology ; Lymph Nodes/pathology ; Lymph Nodes/physiopathology ; Macaca fascicularis ; Macaca mulatta ; RNA, Messenger/analysis ; RNA, Viral/analysis ; Respiratory System/pathology ; Respiratory System/virology ; SARS-CoV-2/immunology ; SARS-CoV-2/physiology ; Virus Replication
Chemical Substances	Antibodies, Viral ; Cytokines ; RNA, Messenger ; RNA, Viral
Language	English
Publishing date	2021-08-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13081673
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Article ; Online: Benefits of increasing the dose of influenza vaccine in residents of long-term care facilities: a randomized placebo-controlled trial.

Cools, Herman J M / Gussekloo, Jacobijn / Remmerswaal, Joyce E M / Remarque, Ed J / Kroes, Aloys C M

Journal of medical virology

2009 Volume 81, Issue 5, Page(s) 908–914

Abstract: Increased vaccine doses and mid-season boosting may increase the proportion of residents with protective immunity from influenza in long-term care facilities. In a multi-center study (1997-1998), 815 residents from 14 long-term care facilities were ... ...

Abstract	Increased vaccine doses and mid-season boosting may increase the proportion of residents with protective immunity from influenza in long-term care facilities. In a multi-center study (1997-1998), 815 residents from 14 long-term care facilities were assigned at random to receive 15 or 30 microg of inactivated influenza vaccine, followed by a 15 microg booster vaccine or a placebo vaccine at Day 84. Seroresponses were re-analyzed by hemagglutination-inhibition (> or =4-fold titer increases, protective titer > or =40, geometric mean titers. Forty percent of the participants had pre-vaccination titers > or =40. At Day 25 after vaccination, this increased to 66.3% after a 15 microg dose versus 73.3% after a dose of 30 microg (P = 0.049). Participants receiving a 30 microg dose followed by a 15 microg booster showed more > or =4-fold titer increases at Day 109 (43.6% vs. 35.4%, P = 0.003) and protective titers > or =40 (74.2% vs. 64.6%, P = 0.041), compared to those receiving only a 15 microg dose. Differences were most apparent in participants with low pre-vaccination titers. Booster vaccination after an initial 15 microg dose of the vaccine did not increase the protective rate (61.9% vs. 63.9% after placebo). The number of participants needed to vaccinate to protect one additional resident by a dose of 15 microg was 4, by a dose of 30 microg 3, and 15 when using a 30 microg dose instead of 15 microg. Doubling the dose of influenza vaccine increased protection-related responses among residents of long-term care facilities, especially in those with low pre-vaccination titers.
MeSH term(s)	Aged ; Aged, 80 and over ; Antibodies, Viral/blood ; Dose-Response Relationship, Immunologic ; Female ; Hemagglutination Inhibition Tests ; Humans ; Immunization, Secondary ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza B virus/immunology ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza, Human/immunology ; Influenza, Human/prevention & control ; Long-Term Care ; Male ; Treatment Outcome ; Vaccination ; Vaccines, Inactivated/administration & dosage ; Vaccines, Inactivated/immunology
Chemical Substances	Antibodies, Viral ; Influenza Vaccines ; Vaccines, Inactivated
Language	English
Publishing date	2009-05
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.21456
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Article: Benefits of increasing the dose of influenza vaccine in residents of long-term care facilities: A randomized placebo-controlled trial

Cools, Herman J.M / Gussekloo, Jacobijn / Remmerswaal, Joyce E.M / Remarque, Ed J / Kroes, Aloys C.M

Journal of medical virology. 2009 May, v. 81, no. 5

2009

Abstract	Increased vaccine doses and mid-season boosting may increase the proportion of residents with protective immunity from influenza in long-term care facilities. In a multi-center study (1997-1998), 815 residents from 14 long-term care facilities were assigned at random to receive 15 or 30 μg of inactivated influenza vaccine, followed by a 15 μg booster vaccine or a placebo vaccine at Day 84. Seroresponses were re-analyzed by hemagglutination-inhibition (greater-than-or-equal4-fold titer increases, protective titer greater-than-or-equal40, geometric mean titers. Forty percent of the participants had pre-vaccination titers greater-than-or-equal40. At Day 25 after vaccination, this increased to 66.3% after a 15 μg dose versus 73.3% after a dose of 30 μg (P = 0.049). Participants receiving a 30 μg dose followed by a 15 μg booster showed more greater-than-or-equal4-fold titer increases at Day 109 (43.6% vs. 35.4%, P = 0.003) and protective titers greater-than-or-equal40 (74.2% vs. 64.6%, P = 0.041), compared to those receiving only a 15 μg dose. Differences were most apparent in participants with low pre-vaccination titers. Booster vaccination after an initial 15 μg dose of the vaccine did not increase the protective rate (61.9% vs. 63.9% after placebo). The number of participants needed to vaccinate to protect one additional resident by a dose of 15 μg was 4, by a dose of 30 μg 3, and 15 when using a 30 μg dose instead of 15 μg. Doubling the dose of influenza vaccine increased protection-related responses among residents of long-term care facilities, especially in those with low pre-vaccination titers. J. Med. Virol. 81:908-914, 2009.
Language	English
Dates of publication	2009-05
Size	p. 908-914.
Publishing place	Wiley Subscription Services, Inc., A Wiley Company
Document type	Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.21456
Database	NAL-Catalogue (AGRICOLA)

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