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  1. Article ; Online: Ally, adversary, or arbitrator? The context-dependent role of eosinophils in vaccination for respiratory viruses and subsequent breakthrough infections.

    Chang, Lauren A / Schotsaert, Michael

    Journal of leukocyte biology

    2024  

    Abstract: Eosinophils are a critical type of immune cell and central players in Type 2 immunity. Existing literature suggests that eosinophils also can play a role in host antiviral responses, typically Type 1 immune events, against multiple respiratory viruses, ... ...

    Abstract Eosinophils are a critical type of immune cell and central players in Type 2 immunity. Existing literature suggests that eosinophils also can play a role in host antiviral responses, typically Type 1 immune events, against multiple respiratory viruses, both directly through release of antiviral mediators and indirectly through activation of other effector cell types. One way to prime host immune responses towards effective antiviral responses is through vaccination, where typically a Type 1-skewed immunity is desirable in the context of intracellular pathogens like respiratory viruses. In the realm of breakthrough respiratory viral infection in vaccinated hosts, an event in which virus can still establish productive infection despite pre-existing immunity, eosinophils are most prominently known for their link to vaccine-associated enhanced respiratory disease (VAERD) upon natural respiratory syncytial virus (RSV) infection. This was observed in a pediatric cohort during the 1960s following vaccination with formalin-inactivated RSV (FI-RSV). More recent research has unveiled additional roles of the eosinophil in respiratory viral infection and breakthrough infection. The specific contribution of eosinophils to the quality of vaccine responses, vaccine efficacy, and antiviral responses to infection in vaccinated hosts remains largely unexplored, especially regarding their potential roles in protection. Based on current findings, we will speculate upon the suggested function of eosinophils and consider the many potential ways by which eosinophils may exert protective and pathological effects in breakthrough infections. We will also discuss how to balance vaccine efficacy with eosinophil-related risks, as well as the use of eosinophils and their products as potential biomarkers of vaccine efficacy or adverse events.
    Language English
    Publishing date 2024-01-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 605722-6
    ISSN 1938-3673 ; 0741-5400
    ISSN (online) 1938-3673
    ISSN 0741-5400
    DOI 10.1093/jleuko/qiae010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Editorial: Pandemic influenza vaccine approaches: Current status and future directions.

    Schotsaert, Michael / Cox, Rebecca Jane / Mallett, Corey P

    Frontiers in immunology

    2022  Volume 13, Page(s) 980956

    MeSH term(s) Humans ; Influenza A Virus, H1N1 Subtype ; Influenza Vaccines ; Influenza, Human/epidemiology ; Influenza, Human/prevention & control ; Pandemics/prevention & control
    Chemical Substances Influenza Vaccines
    Language English
    Publishing date 2022-08-18
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.980956
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Host immune response-inspired development of the influenza vaccine.

    Choi, Angela / García-Sastre, Adolfo / Schotsaert, Michael

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2020  Volume 125, Issue 1, Page(s) 28–35

    Abstract: Objective: To assess the current and future development of influenza vaccines.: Data sources: PubMed searches were performed cross-referencing the keywords influenza, influenza vaccine, host immune response, correlates of protection, vaccine ... ...

    Abstract Objective: To assess the current and future development of influenza vaccines.
    Data sources: PubMed searches were performed cross-referencing the keywords influenza, influenza vaccine, host immune response, correlates of protection, vaccine development, vaccine efficacy. Articles were reviewed for additional citations.
    Study selections: Articles were reviewed and selected on the basis of relevance to subject matter.
    Results: In this review, we first introduce the influenza virus, its nomenclature, and the concepts of antigenic drift and shift. Second, we discuss the status of currently licensed influenza virus vaccines. We briefly focus on influenza vaccine responses beyond hemagglutination inhibition that may correlate with protection against influenza viruses of different subtypes. Third, we explain how studying host responses to influenza infection and vaccination with advanced serologic methods, B-cell receptor sequencing, and transcriptomic profiling can guide the development of improved influenza virus vaccines. Fourth, we provide 2 suggestions on how current influenza vaccines can be optimized by redirecting immune responses toward conserved viral antigens and the use of adjuvants.
    Conclusion: Influenza vaccine design can benefit from novel insights obtained from the study of host responses to influenza virus infection and vaccination. Integration of the large amount of available clinical and preclinical data requires systems approaches that can elucidate novel correlates of protection and will guide further development of influenza vaccine.
    MeSH term(s) Animals ; Humans ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control
    Chemical Substances Influenza Vaccines
    Language English
    Publishing date 2020-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2020.04.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Development of an HIV reporter virus that identifies latently infected CD4

    Kim, Eun Hye / Manganaro, Lara / Schotsaert, Michael / Brown, Brian D / Mulder, Lubbertus C F / Simon, Viviana

    Cell reports methods

    2022  Volume 2, Issue 6, Page(s) 100238

    Abstract: There is no cure for HIV infection, as the virus establishes a latent reservoir, which escapes highly active antiretroviral treatments. One major obstacle is the difficulty identifying cells that harbor latent proviruses. We devised a single-round viral ... ...

    Abstract There is no cure for HIV infection, as the virus establishes a latent reservoir, which escapes highly active antiretroviral treatments. One major obstacle is the difficulty identifying cells that harbor latent proviruses. We devised a single-round viral vector that carries a series of versatile reporter molecules that are expressed in an LTR-dependent or LTR-independent manner and make it possible to accurately distinguish productive from latent infection. Using primary human CD4
    MeSH term(s) Humans ; HIV Infections ; CD4-Positive T-Lymphocytes ; Virus Latency ; HIV-1/genetics ; Proviruses/genetics ; Latent Infection
    Language English
    Publishing date 2022-06-13
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 2667-2375
    ISSN (online) 2667-2375
    DOI 10.1016/j.crmeth.2022.100238
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Influenza breakthrough infection in vaccinated mice is characterized by non-pathological lung eosinophilia.

    Chang, Lauren A / Choi, Angela / Rathnasinghe, Raveen / Warang, Prajakta / Noureddine, Moataz / Jangra, Sonia / Chen, Yong / De Geest, Bruno G / Schotsaert, Michael

    Frontiers in immunology

    2023  Volume 14, Page(s) 1217181

    Abstract: Eosinophils are important mediators of mucosal tissue homeostasis, anti-helminth responses, and allergy. Lung eosinophilia has previously been linked to aberrant Type 2-skewed T cell responses to respiratory viral infection and may also be a consequence ... ...

    Abstract Eosinophils are important mediators of mucosal tissue homeostasis, anti-helminth responses, and allergy. Lung eosinophilia has previously been linked to aberrant Type 2-skewed T cell responses to respiratory viral infection and may also be a consequence of vaccine-associated enhanced respiratory disease (VAERD), particularly in the case of respiratory syncytial virus (RSV) and the formalin-inactivated RSV vaccine. We previously reported a dose-dependent recruitment of eosinophils to the lungs of mice vaccinated with alum-adjuvanted trivalent inactivated influenza vaccine (TIV) following a sublethal, vaccine-matched H1N1 (A/New Caledonia/20/1999; NC99) influenza challenge. Given the differential role of eosinophil subset on immune function, we conducted the investigations herein to phenotype the lung eosinophils observed in our model of influenza breakthrough infection. Here, we demonstrate that eosinophil influx into the lungs of vaccinated mice is adjuvant- and sex-independent, and only present after vaccine-matched sublethal influenza challenge but not in mock-challenged mice. Furthermore, vaccinated and challenged mice had a compositional shift towards more inflammatory eosinophils (iEos) compared to resident eosinophils (rEos), resembling the shift observed in ovalbumin (OVA)-sensitized allergic control mice, however without any evidence of enhanced morbidity or aberrant inflammation in lung cytokine/chemokine signatures. Furthermore, we saw a lung eosinophil influx in the context of a vaccine-mismatched challenge. Additional layers of heterogeneity in the eosinophil compartment were observed via unsupervised clustering analysis of flow cytometry data. Our collective findings are a starting point for more in-depth phenotypic and functional characterization of lung eosinophil subsets in the context of vaccine- and infection-induced immunity.
    MeSH term(s) Animals ; Mice ; Asthma ; Breakthrough Infections ; Hypersensitivity ; Influenza A Virus, H1N1 Subtype ; Influenza Vaccines ; Influenza, Human ; Lung ; Pulmonary Eosinophilia
    Chemical Substances Influenza Vaccines
    Language English
    Publishing date 2023-08-04
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2023.1217181
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Inactivated influenza virus vaccines: the future of TIV and QIV.

    Schotsaert, Michael / García-Sastre, Adolfo

    Current opinion in virology

    2017  Volume 23, Page(s) 102–106

    Abstract: Influenza viruses continue to be a major public health concern, despite the availability of vaccines. Currently licensed influenza vaccines aim at the induction of antibodies that target hemagglutinin, the major antigenic determinant on the surface of ... ...

    Abstract Influenza viruses continue to be a major public health concern, despite the availability of vaccines. Currently licensed influenza vaccines aim at the induction of antibodies that target hemagglutinin, the major antigenic determinant on the surface of influenza virions that is responsible for attachment of the virus to the host cell that is to be infected. Currently licensed influenza vaccines come as inactivated or live attenuated influenza vaccines and are trivalent or quadrivalent as they contain antigens of two influenza A and one or two influenza B strains that circulate in the human population, respectively. In this review we briefly compare trivalent and quadrivalent inactivated influenza vaccines (TIV and QIV) with live attenuated influenza vaccines (LAIV). The use of the latter vaccine type in children age 2-8 has been disrecommended recently by the American Centers for Disease Control and Prevention due to inferior vaccine effectiveness in this age group in recent seasons. This recommendation will favor the use of TIV and QIV over LAIV in the near future. However, there is much evidence from studies in humans that illustrate the benefit of LAIV and we discuss some of the mechanisms that contribute to broader protection against influenza viruses of different subtypes induced by natural infection and LAIV. The future challenge will be to apply these insights to allow induction of broader and long-lasting protection provided by TIV and QIV vaccines, for example, by the use of adjuvants or combining LAIV with TIV and QIV. Other immune factors than serum hemagglutination inhibiting antibodies have shown to correlate with protection provided by TIV and QIV, which illustrates the need for other correlates of protection than hemagglutination inhibition by serum antibodies and justifies more focus on influenza antigens in the TIV and QIV other than hemagglutinin.
    MeSH term(s) Humans ; Influenza Vaccines/administration & dosage ; Influenza Vaccines/immunology ; Influenza, Human/prevention & control ; Vaccines, Attenuated/administration & dosage ; Vaccines, Attenuated/immunology ; Vaccines, Inactivated/administration & dosage ; Vaccines, Inactivated/immunology
    Chemical Substances Influenza Vaccines ; Vaccines, Attenuated ; Vaccines, Inactivated
    Language English
    Publishing date 2017-05-12
    Publishing country Netherlands
    Document type Comparative Study ; Journal Article ; Review
    ZDB-ID 2611378-8
    ISSN 1879-6265 ; 1879-6257
    ISSN (online) 1879-6265
    ISSN 1879-6257
    DOI 10.1016/j.coviro.2017.04.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in QIV vaccinated mice.

    Jangra, Sonia / Lamoot, Alexander / Singh, Gagandeep / Laghlali, Gabriel / Chen, Yong / Yz, Tingting / García-Sastre, Adolfo / De Geest, Bruno G / Schotsaert, Michael

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic ... ...

    Abstract Adjuvants can enhance vaccine effectiveness of currently licensed influenza vaccines. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus derived defective interfering (SDI) RNA, a RIG-I agonist, and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), TLR7/8 adjuvant. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating the direct delivery of a RIG-I agonist to the cytosol. We have previously tested SDI and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated in a licensed vaccine setting (quadrivalent influenza vaccine or QIV) against H1N1 influenza virus, showing robust induction of antibody titres and T cell responses. Depending on the adjuvant combination and LNP lipid composition (K-Ac7-Dsa or S-Ac7-Dog lipids), humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with protection during viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was examined against challenge with the vaccine-matching strain of H1N1 influenza A virus. Groups that received either LNP formulated with SDI, IMDQ-PEG-Chol or both showed very low levels of viral replication in their lungs at five days post virus infection. LNP ionizable lipid composition as well as loading (empty versus SDI) also skewed host responses to infection, as reflected in the cytokine and chemokine levels in lungs of vaccinated animals upon infection. These studies show the potential of LNPs as adjuvant delivery vehicles for licensed vaccines and illustrate the importance of LNP composition for subsequent host responses to infection, an important point of consideration for vaccine safety.
    Language English
    Publishing date 2024-01-15
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.14.575599
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Development of an HIV reporter virus that identifies latently infected CD4+ T cells

    Kim, Eun Hye / Manganaro, Lara / Schotsaert, Michael / Brown, Brian D. / Mulder, Lubbertus C.F. / Simon, Viviana

    Cell reports. 2022 June 20, v. 2, no. 6

    2022  

    Abstract: There is no cure for HIV infection, as the virus establishes a latent reservoir, which escapes highly active antiretroviral treatments. One major obstacle is the difficulty identifying cells that harbor latent proviruses. We devised a single-round viral ... ...

    Abstract There is no cure for HIV infection, as the virus establishes a latent reservoir, which escapes highly active antiretroviral treatments. One major obstacle is the difficulty identifying cells that harbor latent proviruses. We devised a single-round viral vector that carries a series of versatile reporter molecules that are expressed in an LTR-dependent or LTR-independent manner and make it possible to accurately distinguish productive from latent infection. Using primary human CD4⁺ T cells, we show that transcriptionally silent proviruses are found in more than 50% of infected cells. The latently infected cells harbor proviruses but lack evidence for multiple spliced transcripts. LTR-silent integrations occurred to variable degrees in all CD4⁺ T subsets examined, with CD4⁺ TEM and CD4⁺ TREG displaying the highest frequency of latent infections. This viral vector permits the interrogation of HIV latency at single-cell resolution, revealing mechanisms of latency establishment and allowing the characterization of effective latency-reversing agents.
    Keywords HIV infections ; antiretroviral agents ; carrier state ; humans ; proviruses ; transcription (genetics)
    Language English
    Dates of publication 2022-0620
    Publishing place Elsevier Inc.
    Document type Article
    ISSN 2667-2375
    DOI 10.1016/j.crmeth.2022.100238
    Database NAL-Catalogue (AGRICOLA)

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  9. Article ; Online: A High-Resolution Look at Influenza Virus Antigenic Drift.

    Schotsaert, Michael / García-Sastre, Adolfo

    The Journal of infectious diseases

    2016  Volume 214, Issue 7, Page(s) 982

    MeSH term(s) Antigenic Variation ; Antigens, Viral ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Influenza A Virus, H3N2 Subtype ; Influenza, Human ; Orthomyxoviridae
    Chemical Substances Antigens, Viral ; Hemagglutinin Glycoproteins, Influenza Virus
    Language English
    Publishing date 2016-05-06
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiw183
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: The virucidal effects of 405 nm visible light on SARS-CoV-2 and influenza A virus.

    Rathnasinghe, Raveen / Jangra, Sonia / Miorin, Lisa / Schotsaert, Michael / Yahnke, Clifford / Garcίa-Sastre, Adolfo

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 19470

    Abstract: The germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV ... ...

    Abstract The germicidal potential of specific wavelengths within the electromagnetic spectrum is an area of growing interest. While ultra-violet (UV) based technologies have shown satisfactory virucidal potential, the photo-toxicity in humans coupled with UV associated polymer degradation limit their use in occupied spaces. Alternatively, longer wavelengths with less irradiation energy such as visible light (405 nm) have largely been explored in the context of bactericidal and fungicidal applications. Such studies indicated that 405 nm mediated inactivation is caused by the absorbance of porphyrins within the organism creating reactive oxygen species which result in free radical damage to its DNA and disruption of cellular functions. The virucidal potential of visible-light based technologies has been largely unexplored and speculated to be ineffective given the lack of porphyrins in viruses. The current study demonstrated increased susceptibility of lipid-enveloped respiratory pathogens of importance such as SARS-CoV-2 (causative agent of COVID-19) and influenza A virus to 405 nm, visible light in the absence of exogenous photosensitizers thereby indicating a potential alternative porphyrin-independent mechanism of visible light mediated viral inactivation. These results were obtained using less than expected irradiance levels which are considered safe for humans and commercially achievable. Our results support further exploration of the use of visible light technology for the application of continuous decontamination in occupied areas within hospitals and/or infectious disease laboratories, specifically for the inactivation of respiratory pathogens such as SARS-CoV-2 and Influenza A.
    MeSH term(s) Disinfection/instrumentation ; Disinfection/methods ; Dose-Response Relationship, Radiation ; Encephalomyocarditis virus/radiation effects ; Influenza A Virus, H1N1 Subtype/radiation effects ; Light ; SARS-CoV-2/radiation effects ; Time Factors ; Virus Inactivation/radiation effects
    Language English
    Publishing date 2021-09-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-97797-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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