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Article ; Online: Promises and challenges of single-domain antibodies to control influenza.

Matthys, Arne / Saelens, Xavier

2024 Volume 222, Page(s) 105807

Abstract: The World Health Organization advices the use of a quadrivalent vaccine as prophylaxis against influenza, to prevent severe influenza-associated disease and -mortality, and to keep up with influenza antigenic diversity. Different small molecule ... ...

Abstract	The World Health Organization advices the use of a quadrivalent vaccine as prophylaxis against influenza, to prevent severe influenza-associated disease and -mortality, and to keep up with influenza antigenic diversity. Different small molecule antivirals to treat influenza have become available. However, emergence of drug resistant influenza viruses has been observed upon use of these antivirals. An appealing alternative approach to prevent or treat influenza is the use of antibody-based antivirals, such as conventional monoclonal antibodies and single-domain antibodies (sdAbs). The surface of the influenza A and B virion is decorated with hemagglutinin molecules, which act as receptor-binding and membrane fusion proteins and represent the main target of neutralizing antibodies. SdAbs that target influenza A and B hemagglutinin have been described. In addition, sdAbs directed against the influenza A virus neuraminidase have been reported, whereas no sdAbs targeting influenza B neuraminidase have been described to date. SdAbs directed against influenza A matrix protein 2 or its ectodomain have been reported, while no sdAbs have been described targeting the influenza B matrix protein 2. Known for their high specificity, ease of production and formatting, sdAb-based antivirals could be a major leap forward in influenza control.
MeSH term(s)	Humans ; Influenza, Human/drug therapy ; Influenza, Human/prevention & control ; Single-Domain Antibodies ; Antibodies, Viral ; Hemagglutinins ; Neuraminidase/chemistry ; Influenza Vaccines ; Orthomyxoviridae Infections/prevention & control ; Antiviral Agents/pharmacology ; Antiviral Agents/therapeutic use ; Hemagglutinin Glycoproteins, Influenza Virus
Chemical Substances	Single-Domain Antibodies ; Antibodies, Viral ; Hemagglutinins ; Neuraminidase (EC 3.2.1.18) ; Influenza Vaccines ; Antiviral Agents ; Hemagglutinin Glycoproteins, Influenza Virus
Language	English
Publishing date	2024-01-12
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2024.105807
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Article ; Online: The Role of Matrix Protein 2 Ectodomain in the Development of Universal Influenza Vaccines.

Saelens, Xavier

The Journal of infectious diseases

2019 Volume 219, Issue Suppl_1, Page(s) S68–S74

Abstract: The influenza A virus matrix protein 2 ectodomain (M2e) is a universal influenza A vaccine candidate. Numerous studies in laboratory mice, but very few in natural influenza A virus hosts, have demonstrated that M2e-based vaccines can provide protection ... ...

Abstract	The influenza A virus matrix protein 2 ectodomain (M2e) is a universal influenza A vaccine candidate. Numerous studies in laboratory mice, but very few in natural influenza A virus hosts, have demonstrated that M2e-based vaccines can provide protection against any influenza A virus challenge. M2e-based immunity is largely accomplished by IgG and early stage clinical studies have demonstrated that the vaccine is safe. Yet M2e is considered a difficult target to develop as a vaccine: it does not offer sterilizing immunity and its mode of action relies on Fcγ receptor-mediated effector mechanisms, most likely in concert with alveolar macrophages. In a human challenge study with an H3N2 virus, treatment with a monoclonal M2e-specific human IgG was associated with a faster recovery compared to placebo treatment. If the universal influenza vaccine field incorporates this antigen into next generation vaccines, M2e could prove its merit when the next influenza pandemic strikes.
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Viral/immunology ; Antibodies, Viral/therapeutic use ; Antigens, Viral/immunology ; Humans ; Immunoglobulin G/immunology ; Immunoglobulin G/therapeutic use ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/isolation & purification ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Influenza, Human/virology ; Mice ; Open Reading Frames ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/virology ; Pandemics/prevention & control ; Protein Domains/immunology ; Receptors, IgG/immunology ; Viral Matrix Proteins/chemistry ; Viral Matrix Proteins/genetics ; Viral Matrix Proteins/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; Antigens, Viral ; Immunoglobulin G ; Influenza Vaccines ; M2 protein, Influenza A virus ; M2e-HBc influenza vaccine ; Receptors, IgG ; Viral Matrix Proteins
Language	English
Publishing date	2019-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiz003
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Article ; Online: Systematic review and meta-analysis of genome-wide pooled CRISPR screens to identify host factors involved in influenza A virus infection.

Maes, Annabel / Botzki, Alexander / Mathys, Janick / Impens, Francis / Saelens, Xavier

Journal of virology

2024 , Page(s) e0185723

Abstract: The host-virus interactome is increasingly recognized as an important research field to discover new therapeutic targets to treat influenza. Multiple pooled genome-wide CRISPR-Cas screens have been reported to identify new pro- and antiviral host factors ...

Abstract	The host-virus interactome is increasingly recognized as an important research field to discover new therapeutic targets to treat influenza. Multiple pooled genome-wide CRISPR-Cas screens have been reported to identify new pro- and antiviral host factors of the influenza A virus. However, at present, a comprehensive summary of the results is lacking. We performed a systematic review of all reported CRISPR studies in this field in combination with a meta-analysis using the algorithm of meta-analysis by information content (MAIC). Two ranked gene lists were generated based on evidence in 15 proviral and 4 antiviral screens. Enriched pathways in the proviral MAIC results were compared to those of a prior array-based RNA interference (RNAi) meta-analysis. The top 50 proviral MAIC list contained genes whose role requires further elucidation, such as the endosomal ion channel Importance: Viruses rely on host factors for their replication, whereas the host cell has evolved virus restriction factors. These factors represent potential targets for host-oriented antiviral therapies. Multiple pooled genome-wide CRISPR-Cas screens have been reported to identify pro- and antiviral host factors in the context of influenza virus infection. We performed a comprehensive analysis of the outcome of these screens based on the publicly available gene lists, using the recently developed algorithm meta-analysis by information content (MAIC). MAIC allows the systematic integration of ranked and unranked gene lists into a final ranked gene list. This approach highlighted poorly characterized host factors and pathways with evidence from multiple screens, such as the vesicle docking and lipid metabolism pathways, which merit further exploration.
Language	English
Publishing date	2024-04-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01857-23
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Article ; Online: Single-domain antibodies make a difference.

Saelens, Xavier / Schepens, Bert

Science (New York, N.Y.)

2021 Volume 371, Issue 6530, Page(s) 681–682

MeSH term(s)	COVID-19 ; Humans ; SARS-CoV-2 ; Single-Domain Antibodies
Chemical Substances	Single-Domain Antibodies
Language	English
Publishing date	2021-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abg2294
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Article ; Online: One Against All: A Broadly Influenza Neutralizing Man-made Monoclonal Antibody Passes Phase I.

Saelens, Xavier

EBioMedicine

2016 Volume 5, Page(s) 16–17

MeSH term(s)	Antibodies, Monoclonal/immunology ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Cross Reactions ; Epitopes/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Influenza A Virus, H1N1 Subtype/immunology ; Influenza Vaccines ; Influenza, Human/drug therapy ; Mice, Inbred BALB C ; Neutralization Tests ; Orthomyxoviridae Infections/drug therapy
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Antibodies, Viral ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
Language	English
Publishing date	2016-02-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2016.02.036
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Article ; Online: One Against All

Xavier Saelens

EBioMedicine, Vol 5, Iss C, Pp 16-

A Broadly Influenza Neutralizing Man-made Monoclonal Antibody Passes Phase I

2016 Volume 17

Keywords	Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2016-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Cell-Mediated Responses to Human Metapneumovirus Infection.

Ballegeer, Marlies / Saelens, Xavier

Viruses

2020 Volume 12, Issue 5

Abstract: Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, ...

Abstract	Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.
MeSH term(s)	Humans ; Immune Evasion ; Immunity, Cellular ; Immunity, Innate ; Lung/immunology ; Lung/pathology ; Lung/virology ; Metapneumovirus/immunology ; Metapneumovirus/pathogenicity ; Metapneumovirus/physiology ; Paramyxoviridae Infections/immunology ; Paramyxoviridae Infections/pathology ; Paramyxoviridae Infections/virology ; Respiratory Tract Infections/immunology ; Respiratory Tract Infections/pathology ; Respiratory Tract Infections/virology ; Virus Replication
Language	English
Publishing date	2020-05-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v12050542
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Article ; Online: Vaccines against human respiratory syncytial virus in clinical trials, where are we now?

Rossey, Iebe / Saelens, Xavier

Expert review of vaccines

2019 Volume 18, Issue 10, Page(s) 1053–1067

Abstract: ... ...

Abstract	Introduction
MeSH term(s)	Animals ; Clinical Trials as Topic ; Humans ; Respiratory Syncytial Virus Infections/prevention & control ; Respiratory Syncytial Virus Vaccines/immunology ; Respiratory Syncytial Virus, Human/genetics ; Respiratory Syncytial Virus, Human/immunology ; Vaccination ; Vaccines, Attenuated/immunology ; Vaccines, Subunit/immunology
Chemical Substances	Respiratory Syncytial Virus Vaccines ; Vaccines, Attenuated ; Vaccines, Subunit
Language	English
Publishing date	2019-10-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2181284-6
ISSN	1744-8395 ; 1476-0584
ISSN (online)	1744-8395
ISSN	1476-0584
DOI	10.1080/14760584.2019.1675520
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Article ; Online: Anti-neuraminidase and anti-hemagglutinin immune serum can confer inter-lineage cross protection against recent influenza B.

Portela Catani, João Paulo / Ysenbaert, Tine / Smet, Anouk / Vuylsteke, Marnik / Vogel, Thorsten U / Saelens, Xavier

PloS one

2023 Volume 18, Issue 1, Page(s) e0280825

Abstract: Influenza B viruses (IBV) are responsible for a considerable part of the burden caused by influenza virus infections. Since their emergence in the 1980s, the Yamagata and Victoria antigenic lineages of influenza B circulate in alternate patterns across ... ...

Abstract	Influenza B viruses (IBV) are responsible for a considerable part of the burden caused by influenza virus infections. Since their emergence in the 1980s, the Yamagata and Victoria antigenic lineages of influenza B circulate in alternate patterns across the globe. Furthermore, their evolutionary divergence and the appearance of new IBV subclades complicates the prediction of future influenza vaccines compositions. It has been proposed that the addition of the neuraminidase (NA) antigen could potentially induce a broader protection and compensate for hemagglutinin (HA) mismatches in the current vaccines. Here we show that anti-NA and -HA sera against both Victoria and Yamagata lineages have limited inter-lineage cross-reactivity. When transferred to mice prior to infection with a panel of IBVs, anti-NA sera were as potent as anti-HA sera in conferring protection against homologous challenge and, in some cases, conferred superior protection against challenge with heterologous IBV strains.
MeSH term(s)	Animals ; Humans ; Mice ; Antibodies, Viral ; Cross Protection ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Immune Sera ; Influenza B virus ; Influenza, Human/prevention & control ; Neuraminidase ; Orthomyxoviridae Infections
Chemical Substances	Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Hemagglutinins ; Immune Sera ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0280825
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Article ; Online: New antibody-based prevention and treatment options for influenza.

Sedeyn, Koen / Saelens, Xavier

Antiviral research

2019 Volume 170, Page(s) 104562

Abstract: The antigenic diversity of human influenza viruses represents a challenge to the development of vaccines with durable immune protection. In addition, small molecule anti-influenza viral drugs can bring clinical relief to influenza patients but the ... ...

Abstract	The antigenic diversity of human influenza viruses represents a challenge to the development of vaccines with durable immune protection. In addition, small molecule anti-influenza viral drugs can bring clinical relief to influenza patients but the emergence of drug resistant viruses can rapidly limit the effectiveness of such drugs. In the past decade, a number of human monoclonal antibodies have been described that can bind to and neutralize a broad range of influenza A and B viruses. Most of these monoclonal antibodies are directed against the viral hemagglutinin (HA) stalk and some have now been evaluated in early to mid-stage clinical trials. An important conclusion from these clinical studies is that hemagglutinin stalk-specific antibodies are safe and can reduce influenza symptoms. In addition, examples of bi- and multi-specific anti-influenza antibodies are discussed, although such antibodies have not yet progressed into clinical testing. In the future, antibody-based therapies might become part of our arsenal to prevent and treat influenza.
MeSH term(s)	Animals ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/immunology ; Binding Sites, Antibody ; Clinical Trials as Topic ; Cross Reactions ; Epitopes/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Influenza, Human/therapy ; Mice ; Orthomyxoviridae ; Orthomyxoviridae Infections/prevention & control ; Orthomyxoviridae Infections/therapy
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Neutralizing ; Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
Language	English
Publishing date	2019-07-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	306628-9
ISSN	1872-9096 ; 0166-3542
ISSN (online)	1872-9096
ISSN	0166-3542
DOI	10.1016/j.antiviral.2019.104562
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