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Article ; Online: Editorial: Novel Concepts in Using Broadly Neutralizing Antibodies for HIV-1 Treatment and Prevention.

Wagh, Kshitij / van Gils, Marit J / Gristick, Harry / Schommers, Philipp

2021 Volume 12, Page(s) 823576

MeSH term(s)	Animals ; Broadly Neutralizing Antibodies/therapeutic use ; HIV Infections/therapy ; HIV-1 ; Humans
Chemical Substances	Broadly Neutralizing Antibodies
Language	English
Publishing date	2021-12-21
Publishing country	Switzerland
Document type	Editorial ; Introductory 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.2021.823576
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Article ; Online: The potential of engineered antibodies for HIV-1 therapy and cure.

Grobben, Marloes / Stuart, Richard Al / van Gils, Marit J

Current opinion in virology

2019 Volume 38, Page(s) 70–80

Abstract: Broadly neutralizing antibodies (bnAbs) are currently under investigation as a therapy for HIV-1 infection and recent clinical trials have shown prolonged viral suppression by bnAbs during antiretroviral treatment interruption. Interestingly, these bnAbs ...

Abstract	Broadly neutralizing antibodies (bnAbs) are currently under investigation as a therapy for HIV-1 infection and recent clinical trials have shown prolonged viral suppression by bnAbs during antiretroviral treatment interruption. Interestingly, these bnAbs also showed the ability to activate the host immune system to clear HIV-1 infected cells. There are many possibilities to further increase the potential efficacy of bnAbs. Most notably, Fc domain engineering to improve half-life and increase engagement of effector cells will augment two advantages of bnAbs. Moreover, antibody engineering can improve affinity and recognition of conserved epitopes and allows the combination of multiple epitope specificities in a single molecule. These increasingly potent and broad antibodies may prove valuable as alternative HIV-1 therapeutic and possibly in curative approaches.
MeSH term(s)	Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing ; Antiretroviral Therapy, Highly Active ; Clinical Trials as Topic ; Genetic Engineering ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/drug effects ; HIV-1/immunology ; Humans ; Treatment Outcome
Chemical Substances	Anti-HIV Agents ; Antibodies, Monoclonal ; Antibodies, Neutralizing
Language	English
Publishing date	2019-08-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2611378-8
ISSN	1879-6265 ; 1879-6257
ISSN (online)	1879-6265
ISSN	1879-6257
DOI	10.1016/j.coviro.2019.07.007
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Article ; Online: A panel of hepatitis C virus glycoproteins for the characterization of antibody responses using antibodies with diverse recognition and neutralization patterns.

Chumbe, Ana / Grobben, Marloes / Capella-Pujol, Joan / Koekkoek, Sylvie M / Zon, Ian / Slamanig, Stefan / Merat, Sabrina J / Beaumont, Tim / Sliepen, Kwinten / Schinkel, Janke / van Gils, Marit J

Virus research

2024 Volume 341, Page(s) 199308

Abstract: A vaccine against Hepatitis C virus (HCV) is urgently needed to limit the spread of HCV. The large antigenic diversity of the HCV glycoprotein E1E2 makes it difficult to design a vaccine but also to fully understand the antibody response after infection ... ...

Abstract	A vaccine against Hepatitis C virus (HCV) is urgently needed to limit the spread of HCV. The large antigenic diversity of the HCV glycoprotein E1E2 makes it difficult to design a vaccine but also to fully understand the antibody response after infection or vaccination. Here we designed a panel of HCV pseudoparticles (HCVpps) that cover a wide range of genetically and antigenically diverse E1E2s. We validate our panel using neutralization and a binding antibody multiplex assay (BAMA). The panel of HCVpps includes E1E2 glycoproteins from acute and chronically infected cases in the Netherlands, as well as E1E2 glycoproteins from previously reported HCVs. Using eight monoclonal antibodies targeting multiple antigenic regions on E1E2, we could categorize four groups of neutralization sensitive viruses with viruses showing neutralization titers over a 100-fold range. One HCVpp (AMS0230) was extremely neutralization resistant and only neutralized by AR4-targeting antibodies. In addition, using binding antibody multiplex competition assay, we delineated mAb epitopes and their interactions. The binding and neutralization sensitivity of the HCVpps were confirmed using patient sera. At the end, eleven HCVpps with unique antibody binding and neutralization profiles were selected as the final panel for standardized HCV antibody assessments. In conclusion, this HCVpp panel can be used to evaluate antibody binding and neutralization breadth and potency as well as delineate the epitopes targeted in sera from patients or candidate vaccine trials. The HCVpp panel in combination with the established antibody competition assay present highly valuable tools for HCV vaccine development and evaluation.
MeSH term(s)	Humans ; Hepacivirus ; Antibodies, Neutralizing ; Antibody Formation ; Neutralization Tests ; Viral Envelope Proteins ; Hepatitis C ; Glycoproteins ; Epitopes ; Hepatitis C Antibodies ; Antibodies, Monoclonal ; Vaccines
Chemical Substances	Antibodies, Neutralizing ; Viral Envelope Proteins ; Glycoproteins ; Epitopes ; Hepatitis C Antibodies ; Antibodies, Monoclonal ; Vaccines
Language	English
Publishing date	2024-01-11
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	605780-9
ISSN	1872-7492 ; 0168-1702
ISSN (online)	1872-7492
ISSN	0168-1702
DOI	10.1016/j.virusres.2024.199308
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Article ; Online: Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies.

Bermejo-Jambrina, Marta / van der Donk, Lieve Eh / van Hamme, John L / Wilflingseder, Doris / de Bree, Godelieve / Prins, Maria / de Jong, Menno / Nieuwkerk, Pythia / van Gils, Marit J / Kootstra, Neeltje A / Geijtenbeek, Teunis Bh

The EMBO journal

2024 Volume 43, Issue 7, Page(s) 1135–1163

Abstract: Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the ... ...

Abstract	Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Antibodies, Viral ; Complement System Proteins ; Inflammation ; Immunity, Innate
Chemical Substances	Antibodies, Viral ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2024-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.1038/s44318-024-00061-0
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Article ; Online: HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth.

van Schooten, Jelle / van Gils, Marit J

Retrovirology

2018 Volume 15, Issue 1, Page(s) 74

Abstract: Despite enormous efforts no HIV-1 vaccine has been developed that elicits broadly neutralizing antibodies (bNAbs) to protect against infection to date. The high antigenic diversity and dense N-linked glycan armor, which covers nearly the entire HIV-1 ... ...

Abstract	Despite enormous efforts no HIV-1 vaccine has been developed that elicits broadly neutralizing antibodies (bNAbs) to protect against infection to date. The high antigenic diversity and dense N-linked glycan armor, which covers nearly the entire HIV-1 envelope protein (Env), are major roadblocks for the development of bNAbs by vaccination. In addition, the naive human antibody repertoire features a low frequency of exceptionally long heavy chain complementary determining regions (CDRH3s), which is a typical characteristic that many HIV-1 bNAbs use to penetrate the glycan armor. Native-like Env trimer immunogens can induce potent but strain-specific neutralizing antibody responses in animal models but how to overcome the many obstacles towards the development of bNAbs remains a challenge. Here, we review recent HIV-1 Env immunization studies and discuss strategies to guide strain-specific antibody responses towards neutralization breadth.
MeSH term(s)	AIDS Vaccines/immunology ; Animals ; Antibodies, Neutralizing/immunology ; Antibody Formation ; Antigenic Variation/immunology ; Epitopes/immunology ; HIV Antibodies/immunology ; HIV Envelope Protein gp120/immunology ; HIV Infections/immunology ; HIV Infections/prevention & control ; HIV-1 ; Humans ; Immunization ; Mice ; env Gene Products, Human Immunodeficiency Virus/immunology
Chemical Substances	AIDS Vaccines ; Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; HIV Envelope Protein gp120 ; env Gene Products, Human Immunodeficiency Virus
Language	English
Publishing date	2018-11-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1742-4690
ISSN (online)	1742-4690
DOI	10.1186/s12977-018-0457-7
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Article ; Online: Hitting HIV's Harpoon.

van Gils, Marit J / Sanders, Rogier W

Immunity

2018 Volume 49, Issue 1, Page(s) 14–15

Abstract: The HIV-1 fusion peptide is a target for broadly neutralizing antibodies. In a recent issue of Nature Medicine, Xu et al. (2018) provide proof-of-concept that vaccination with fusion peptide followed by vaccination with an envelope glycoprotein trimer ... ...

Abstract	The HIV-1 fusion peptide is a target for broadly neutralizing antibodies. In a recent issue of Nature Medicine, Xu et al. (2018) provide proof-of-concept that vaccination with fusion peptide followed by vaccination with an envelope glycoprotein trimer can induce antibodies in animal models that neutralize diverse HIV-1 viruses.
MeSH term(s)	AIDS Vaccines ; Animals ; Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; HIV Infections ; HIV-1/immunology ; Peptides
Chemical Substances	AIDS Vaccines ; Antibodies, Neutralizing ; Epitopes ; HIV Antibodies ; Peptides
Language	English
Publishing date	2018-07-17
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2018.07.003
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Human Milk Antibody Response After Combining Two Different COVID-19 Vaccines: Mix-and-Match.

Mulleners, Sien J / Juncker, Hannah G / van Gils, Marit J / van Goudoever, Johannes B / van Keulen, Britt J

Journal of human lactation : official journal of International Lactation Consultant Association

2022 Volume 38, Issue 3, Page(s) 401–406

Abstract: Background: SARS-CoV-2-specific antibodies are secreted into human milk after women are vaccinated against COVID-19, which might protect the breastfed infant. Due to several reports of severe side-effects of the Oxford-AstraZeneca ChAdOx1 (AZD1222) ... ...

Abstract	Background: SARS-CoV-2-specific antibodies are secreted into human milk after women are vaccinated against COVID-19, which might protect the breastfed infant. Due to several reports of severe side-effects of the Oxford-AstraZeneca ChAdOx1 (AZD1222) vaccine against COVID-19, some lactating women followed a heterologous vaccination schedule consisting of the first dose of AZD1222 and a second dose of an mRNA-based vaccine. However, it is unclear whether this generates a significant SARS-CoV-2-specific antibody response in human milk. Main issue: To quantify the SARS-CoV-2-specific antibody response in human milk of two lactating women receiving a heterologous vaccination schedules: AZD1222 and mRNA-based vaccine (Pfizer-BioNTech [BNT162b2] and Moderna [mRNA-1273]). Management: Both participants collected 16 samples of human milk longitudinally. SARS-CoV-2-specific Immunoglobulin A was measured using an enzyme-linked immunosorbent assay. Conclusion: Based on our results, it could be suggested that heterologous vaccination with AZD1222 and an mRNA-based vaccine can elicit a significant SARS-CoV-2 specific IgA response in human milk.
MeSH term(s)	Antibodies, Viral ; Antibody Formation ; BNT162 Vaccine ; Breast Feeding ; COVID-19/prevention & control ; COVID-19 Vaccines ; ChAdOx1 nCoV-19 ; Female ; Humans ; Lactation ; Milk, Human ; RNA, Messenger ; SARS-CoV-2 ; Viral Vaccines/pharmacology
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines ; RNA, Messenger ; Viral Vaccines ; ChAdOx1 nCoV-19 (B5S3K2V0G8) ; BNT162 Vaccine (N38TVC63NU)
Language	English
Publishing date	2022-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1138470-0
ISSN	1552-5732 ; 0890-3344
ISSN (online)	1552-5732
ISSN	0890-3344
DOI	10.1177/08903344221103260
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Article ; Online: Optimization of Anti-SARS-CoV-2 Neutralizing Antibody Therapies: Roadmap to Improve Clinical Effectiveness and Implementation.

van der Straten, Karlijn / van Gils, Marit J / de Taeye, Steven W / de Bree, Godelieve J

Frontiers in medical technology

2022 Volume 4, Page(s) 867982

Abstract: One of the major breakthroughs to combat the current Coronavirus Disease 2019 (COVID-19) pandemic has been the development of highly effective vaccines against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Still, alternatives are ... ...

Abstract	One of the major breakthroughs to combat the current Coronavirus Disease 2019 (COVID-19) pandemic has been the development of highly effective vaccines against the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Still, alternatives are needed for individuals who are at high risk of developing severe COVID-19 and are not protected by vaccination. Monoclonal antibodies against the spike protein of SARS-CoV-2 have been shown to be effective as prophylaxis and treatment against COVID-19. However, the emergence of variants of concern (VOCs) challenges the efficacy of antibody therapies. This review describes the neutralization resistance of the clinically-approved monoclonal antibody therapies against the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P1), Delta (B.1.617.2), and the Omicron (B.1.1.529) variants. To guide the development of monoclonal antibody therapies and to anticipate on the continuous evolution of SARS-CoV-2, we highlight different strategies to broaden the antibody activity by targeting more conserved epitopes and/or simultaneously targeting multiple sites of vulnerability of the virus. This review further describes the contribution of antibody Fc effector functions to optimize the antibody efficacy. In addition, the main route of SARS-CoV-2 antibody administration is currently intravenously and dictates a monthly injection when used as prophylactic. Therefore, we discusses the concept of long-acting antibodies (LAABs) and non-intravenously routes of antibody administration in order to broaden the clinical applicability of antibody therapies.
Language	English
Publishing date	2022-03-28
Publishing country	Switzerland
Document type	Journal Article ; Review
ISSN	2673-3129
ISSN (online)	2673-3129
DOI	10.3389/fmedt.2022.867982
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Article: Maternal Stress and Human Milk Antibodies During the COVID-19 Pandemic.

Juncker, Hannah G / Ruhé, Eliza J M / Korosi, Aniko / van Goudoever, Johannes B / van Gils, Marit J / van Keulen, Britt J

Frontiers in nutrition

2022 Volume 9, Page(s) 923501

Abstract: Importance: SARS-CoV-2: Objective: To determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of : Design: Population-based prospective cohort study.!# ...

Abstract	Importance: SARS-CoV-2 Objective: To determine whether psychological stress is increased in lactating women during the COVID-19 pandemic, and if maternal stress is associated with the level of Design: Population-based prospective cohort study. Setting: Data collection took place in the Netherlands between October 2020 and February 2021. Participants: Lactating women living in the Netherlands were eligible to participate in this study. In total, 2310 women were included. Exposures: Stress exposure during the COVID-19 pandemic was determined using the Perceived Stress Scale (PSS) questionnaire and maternal lifetime stress was determined by the Life Stressor Checklist - revised (LSC-r) questionnaire. Main outcomes and measures: Stress experience during the COVID-19 pandemic was compared with a pre-pandemic cohort. Results: The PSS score of lactating mothers was not increased during the pandemic compared to the PSS score in the prepandemic cohort. Six hundred ninety-one participants had Conclusions and relevance: Our results suggest that lactating women in the Netherlands did not experience higher stress levels during the COVID-19 pandemic. Breastfed infants of mothers with high chronic stress levels receive lower amounts of antibodies through human milk, which possibly makes them more vulnerable to respiratory infections. This emphasizes the importance of psychological wellbeing during lactation.
Language	English
Publishing date	2022-06-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2776676-7
ISSN	2296-861X
ISSN	2296-861X
DOI	10.3389/fnut.2022.923501
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Article ; Online: Comparing Human Milk Antibody Response After 4 Different Vaccines for COVID-19.

Juncker, Hannah G / Mulleners, Sien J / Coenen, Esmée R M / van Goudoever, Johannes B / van Gils, Marit J / van Keulen, Britt J

JAMA pediatrics

2022 Volume 176, Issue 6, Page(s) 611–612

MeSH term(s)	Antibodies, Viral ; Antibody Formation ; COVID-19/prevention & control ; COVID-19 Vaccines ; Humans ; Milk, Human ; SARS-CoV-2 ; Vaccination
Chemical Substances	Antibodies, Viral ; COVID-19 Vaccines
Language	English
Publishing date	2022-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701223-2
ISSN	2168-6211 ; 2168-6203
ISSN (online)	2168-6211
ISSN	2168-6203
DOI	10.1001/jamapediatrics.2022.0084
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