Publications of Laurent Gillet
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See detailKinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects
Desmecht, Salomé ULiege; Tashkeev, Aleksandr ULiege; Nicole Marechal, Nicole et al

E-print/Working paper (2022)

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of ... [more ▼]

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liège University Hospital (CHU) of Liège in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naïve (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN- on peripheral blood lymphocytes using the QuantiFERON Human IFN- SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naïve HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses. [less ▲]

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See detailThe First Random Observational Survey of Barrier Gestures against COVID-19
Renault, Véronique ULiege; Humblet, Marie-France ULiege; Parisi, Gianni ULiege et al

in International Journal of Environmental Research and Public Health (2021), 18(19), 9972

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See detailIn-Depth Longitudinal Comparison of Clinical Specimens to Detect SARS-CoV-2.
Defêche, Justine ULiege; AZARZAR, Samira ULiege; Mesdagh, Alyssia ULiege et al

in Pathogens (Basel, Switzerland) (2021), 10(11),

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 ... [more ▼]

The testing and isolation of patients with coronavirus disease 2019 (COVID-19) are indispensable tools to control the ongoing COVID-19 pandemic. PCR tests are considered the "gold standard" of COVID-19 testing and mostly involve testing nasopharyngeal swab specimens. Our study aimed to compare the sensitivity of tests for various sample specimens. Seventy-five participants with confirmed COVID-19 were included in the study. Nasopharyngeal swabs, oropharyngeal swabs, Oracol-collected saliva, throat washes and rectal specimens were collected along with pooled swabs. Participants were asked to complete a questionnaire to correlate specific clinical symptoms and the symptom duration with the sensitivity of detecting COVID-19 in various sample specimens. Sampling was repeated after 7 to 10 days (T2), then after 14 to 20 days (T3) to perform a longitudinal analysis of sample specimen sensitivity. At the first time point, the highest percentages of SARS-CoV-2-positive samples were observed for nasopharyngeal samples (84.3%), while 74%, 68.2%, 58.8% and 3.5% of throat washing, Oracol-collected saliva, oropharyngeal and rectal samples tested positive, respectively. The sensitivity of all sampling methods except throat wash samples decreased rapidly at later time points compared to the first collection. The throat washing method exhibited better performance than the gold standard nasopharyngeal swab at the second and third time points after the first positive test date. Nasopharyngeal swabs were the most sensitive specimens for early detection after symptom onset. Throat washing is a sensitive alternative method. It was found that SARS-CoV-2 persists longer in the throat and saliva than in the nasopharynx. [less ▲]

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See detailSingle-Virus Force Spectroscopy Discriminates the Intrinsic Role of Two Viral Glycoproteins upon Cell Surface Attachment.
Delguste, Martin; Brun, Grégoire Le; Cotin, Florian et al

in Nano Letters (2021), 21(1), 847-853

Viruses are one of the most efficient pathogenic entities on earth, resulting from millions of years of evolution. Each virus particle carries the minimum number of genes and proteins to ensure their ... [more ▼]

Viruses are one of the most efficient pathogenic entities on earth, resulting from millions of years of evolution. Each virus particle carries the minimum number of genes and proteins to ensure their reproduction within host cells, hijacking some host replication machinery. However, the role of some viral proteins is not yet unraveled, with some appearing even redundant. For example, murid herpesvirus 4, the current model for human gammaherpesvirus infection, can bind to cell surface glycosaminoglycans using both glycoproteins gp70 and gH/gL. Here, using atomic force microscopy, we discriminate their relative contribution during virus binding to cell surface glycosaminoglycans. Single-virus force spectroscopy experiments demonstrate that gH/gL is the main actor in glycosaminoglycan binding, engaging more numerous and more stable interactions. We also demonstrated that Fab antibody fragments targeting gH/gL or gp70 appear to be a promising treatment to prevent the attachment of virions to cell surfaces. [less ▲]

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See detailLy6Chi monocytes are key immunoregulators of gammaherpesvirus infection
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Conference (2020, December 18)

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See detailLy6Chi monocytes are key immunoregulators of gammaherpesvirus infection
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Conference (2020, November 20)

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See detailA gammaherpesvirus licenses CD8 T cells to protect the host from pneumovirus-induced immunopathologies.
Dourcy, Mickael ULiege; Maquet, Céline ULiege; Dams, Lorène ULiege et al

in Mucosal Immunology (2020)

Human respiratory syncytial virus (RSV) is a pneumovirus that causes severe infections in infants worldwide. Despite intensive research, safe and effective vaccines against RSV have remained elusive. The ... [more ▼]

Human respiratory syncytial virus (RSV) is a pneumovirus that causes severe infections in infants worldwide. Despite intensive research, safe and effective vaccines against RSV have remained elusive. The main reason is that RSV infection of children previously immunized with formalin-inactivated-RSV vaccines has been associated with exacerbated pathology, a phenomenon called RSV vaccine-enhanced respiratory disease. In parallel, despite the high RSV prevalence, only a minor proportion of children develop severe diseases. Interestingly, variation in the immune responses against RSV or following RSV vaccination could be linked with differences of exposure to microbes during childhood. Gammaherpesviruses (γHVs), such as the Epstein–Barr virus, are persistent viruses that deeply influence the immune system of their host and could therefore affect the development of pneumovirus-induced immunopathologies for the long term. Here, we showed that a previous ɣHV infection protects against both pneumovirus vaccine-enhanced disease and pneumovirus primary infection and that CD8 T cells are essential for this protection. These observations shed a new light on the understanding of pneumovirus-induced diseases and open new perspectives for the development of vaccine strategies. [less ▲]

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See detailInitial Step of Virus Entry: Virion Binding to Cell-Surface Glycans.
Koehler, Melanie; Delguste, Martin; Sieben, Christian et al

in Annual review of virology (2020)

Virus infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and cell ... [more ▼]

Virus infection is an intricate process that requires the concerted action of both viral and host cell components. Entry of viruses into cells is initiated by interactions between viral proteins and cell-surface receptors. Various cell-surface glycans function as initial, usually low-affinity attachment factors, providing a first anchor of the virus to the cell surface, and further facilitate high-affinity binding to virus-specific cell-surface receptors, while other glycans function as specific entry receptors themselves. It is now possible to rapidly identify specific glycan receptors using different techniques, define atomic-level structures of virus-glycan complexes, and study these interactions at the single-virion level. This review provides a detailed overview of the role of glycans in viral infection and highlights experimental approaches to study virus-glycan binding along with specific examples. In particular, we highlight the development of the atomic force microscope to investigate interactions with glycans at the single-virion level directly on living mammalian cells, which offers new perspectives to better understand virus-glycan interactions in physiologically relevant conditions. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates. [less ▲]

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See detailLy6Chi monocytes are key orchestrators of gammaherpesvirus lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Conference (2019, December 19)

Detailed reference viewed: 24 (5 ULiège)
See detailLy6Chi monocytes are key orchestrators of gammaherpesvirus lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Conference (2019, November 14)

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See detailRole of monocytes in Murid gammaherpesvirus 4 lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Conference (2019, November 08)

Detailed reference viewed: 18 (2 ULiège)
See detailLy6Chi monocytes are key orchestrators of gammaherpesvirus lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Poster (2019, September 13)

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See detailFunction of monocytes in Murid herpesvirus 4 lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Poster (2019, May 21)

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See detailFunction of monocytes in Murid herpesvirus 4 lifecycle
Maquet, Céline ULiege; Loos, Pauline ULiege; Javaux, Justine ULiege et al

Poster (2019, February 21)

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See detailIFN-lambda Decreases Murid Herpesvirus-4 Infection of the Olfactory Epithelium but Fails to Prevent Virus Reactivation in the Vaginal Mucosa.
Jacobs, Sophie; Zeippen, Caroline ULiege; Wavreil, Fanny et al

in Viruses (2019), 11(8),

Murid herpesvirus-4 (MuHV-4), a natural gammaherpesvirus of rodents, can infect the mouse through the nasal mucosa, where it targets sustentacular cells and olfactory neurons in the olfactory epithelium ... [more ▼]

Murid herpesvirus-4 (MuHV-4), a natural gammaherpesvirus of rodents, can infect the mouse through the nasal mucosa, where it targets sustentacular cells and olfactory neurons in the olfactory epithelium before it propagates to myeloid cells and then to B cells in lymphoid tissues. After establishment of latency in B cells, viral reactivation occurs in the genital tract in 80% of female mice, which can lead to spontaneous sexual transmission to co-housed males. Interferon-lambda (IFN-lambda) is a key player of the innate immune response at mucosal surfaces and is believed to limit the transmission of numerous viruses by acting on epithelial cells. We used in vivo plasmid-mediated IFN-lambda expression to assess whether IFN-lambda could prophylactically limit MuHV-4 infection in the olfactory and vaginal mucosae. In vitro, IFN-lambda decreased MuHV-4 infection in cells that overexpressed IFN-lambda receptor 1 (IFNLR1). In vivo, prophylactic IFN-lambda expression decreased infection of the olfactory epithelium but did not prevent virus propagation to downstream organs, such as the spleen where the virus establishes latency. In the olfactory epithelium, sustentacular cells readily responded to IFN-lambda. In contrast, olfactory neurons did not respond to IFN-lambda, thus, likely allowing viral entry. In the female genital tract, columnar epithelial cells strongly responded to IFN-lambda, as did most vaginal epithelial cells, although with some variation from mouse to mouse. IFN-lambda expression, however, failed to prevent virus reactivation in the vaginal mucosa. In conclusion, IFN-lambda decreased MuHV-4 replication in the upper respiratory epithelium, likely by protecting the sustentacular epithelial cells, but it did not protect olfactory neurons and failed to block virus reactivation in the genital mucosa. [less ▲]

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See detailOral vaccination with replication-competent adenovirus in mice reveals the dissemination of the viral vaccine beyond the gastrointestinal tract.
Goffin, Emeline ULiege; Javaux, Justine; Destexhe, Eric et al

in Journal of virology (2019)

Since the 1970s, replication-competent human adenoviruses 4 and 7 have been used as oral vaccines to protect US soldiers against the severe respiratory diseases caused by these viruses. These vaccines are ... [more ▼]

Since the 1970s, replication-competent human adenoviruses 4 and 7 have been used as oral vaccines to protect US soldiers against the severe respiratory diseases caused by these viruses. These vaccines are thought to establish a digestive tract infection conferring protection against respiratory challenge through antibodies. The success of these vaccines makes replication-competent adenoviruses attractive candidates for use as oral vaccine vectors. However, the inability of human adenoviruses to replicate efficiently in laboratory animals has hampered the study of such vectors. Here, we used mouse adenovirus type 1 (MAV-1) in mice to study oral replication-competent adenovirus-based vaccines. We showed that MAV-1 oral administration recapitulates the protection against homologous respiratory challenge observed with adenoviruses 4 and 7 vaccines. Moreover, live oral MAV-1 vaccine better protected against a respiratory challenge than inactivated vaccines. This protection was linked not only with the presence of MAV-1-specific antibodies but also with a better recruitment of effector CD8 T cells. However, unexpectedly, we found that such oral replication-competent vaccine systemically spread all over the body. Our results therefore support using MAV-1 to study replication-competent oral adenovirus-based vaccines but also highlight the fact that those vaccines could disseminate widely in the body.IMPORTANCE Replication-competent adenoviruses appear to be promising vectors for the development of oral vaccines in humans. However, study and development of these vaccines suffer from the lack of any reliable animal model. In this study, mouse adenovirus type 1 has been used to develop a small animal model for oral replication-competent adenovirus vaccines. While this model reproduced in mice what is observed with human adenovirus oral vaccines, it also highlighted that oral immunization with such replication-competent vaccine is associated with the systemic spread of the virus. This study is therefore of major importance for the future development of such vaccine platforms and their use in large human populations. [less ▲]

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