Karl Stefic

Dr. Karl Stefic

orcid

Research Focus & Metrics

Academic Career Length

11Years (2016-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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12 February 2021 in bioRxiv
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DPDelphine Planas
Delphine Planas
TBTimothée Bruel
Timothée Bruel
LGLudivine Grzelak
Ludivine Grzelak
FGFlorence Guivel-Benhassine
Florence Guivel-Benhassine
ISIsabelle Staropoli
Isabelle Staropoli
OSOlivier Schwartz
Olivier Schwartz
SARS-CoV-2 B.1.1.7 and B.1.351 variants emerged respectively in United Kingdom and South Africa and spread in many countries. Here, we isolated infectious B.1.1.7 and B.1.351 strains and examined their sensitivity to anti-SARS-CoV-2 antibodies present in sera and nasal swabs, in comparison with a D614G reference virus. We established a novel rapid neutralization assay, based on reporter cells that become GFP+ after overnight infection. B.1.1.7 was neutralized by 79/83 sera from convalescent patients collected up to 9 months post symptoms, almost similar to D614G. There was a mean 6-fold reduction in titers and even loss of activity against B.1.351 in 40% of convalescent sera after 9 months. Early sera from 19 vaccinated individuals were almost as potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Nasal swabs from vaccine recipients were not neutralizing, except in individuals who were diagnosed COVID-19+ before vaccination. Thus, faster-spreading variants acquired a partial resistance to humoral immunity generated by natural infection or vaccination, mostly visible in individuals with low antibody levels.

28 March 2024 in The Journal of Infectious Diseases
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Journal Article
Open access
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Margarida SimõesMargarida Simões
Margarida Simões
EHEmma B. Hodcroft
Emma B. Hodcroft
PSPeter Simmonds
Peter Simmonds
JAJan Albert
Jan Albert
EAEnagnon K Alidjinou
Enagnon K Alidjinou
KBKimberley S M Benschop
Kimberley S M Benschop
Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021–2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0–5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages.

23 September 2021 in Vaccines
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Journal Article
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JMJulien Marlet
Julien Marlet
PGPhilippe Gatault
Philippe Gatault
ZMZoha Maakaroun
Zoha Maakaroun
HLHélène Longuet
Hélène Longuet
KSKarl Stefic
Karl Stefic
CGCatherine Gaudy-Graffin
Catherine Gaudy-Graffin
The impact of a third dose of COVID-19 vaccine on antibody responses is unclear in immunocompromised patients. The objective of this retrospective study was to characterize antibody responses induced by a third dose of mRNA COVID-19 vaccine in 160 kidney transplant recipients and 20 patients treated for chronic lymphocytic leukemia (CLL). Prevalence of anti-spike IgG ≥ 7.1 and ≥ 30 BAU/mL after the third dose were 47% (75/160) and 39% (63/160) in kidney transplant recipients, and 57% (29/51) and 50% (10/20) in patients treated for CLL. Longitudinal follow-up identified a moderate increase in SARS-CoV-2 anti-spike IgG levels after a third dose of vaccine in kidney transplant recipients (0.19 vs. 5.28 BAU/mL, p = 0.03) and in patients treated for CLL (0.63 vs. 10.7 BAU/mL, p = 0.0002). This increase in IgG levels had a limited impact on prevalence of anti-spike IgG ≥ 30 BAU/mL in kidney transplant recipients (17%, 2/12 vs. 33%, 4/12, p = 0.64) and in patients treated for CLL (5%, 1/20 vs. 45%, 9/20, p = 0.008). These results highlight the need for vaccination of the general population and the importance of non-medical preventive measures to protect immunocompromised patients.

2 February 2022 in Nature Communications
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Journal Article
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JDJérémy Dufloo
Jérémy Dufloo
CPCyril Planchais
Cyril Planchais
SFStéphane Frémont
Stéphane Frémont
VLValérie Lorin
Valérie Lorin
FGFlorence Guivel-Benhassine
Florence Guivel-Benhassine
TBTimothée Bruel
Timothée Bruel
Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. Beyond neutralization, bNAbs exert Fc-dependent functions including antibody-dependent cellular cytotoxicity and activation of the complement. Here, we show that a subset of bNAbs targeting the CD4 binding site and the V1/V2 or V3 loops inhibit viral release from infected cells. We combined immunofluorescence, scanning electron microscopy, transmission electron microscopy and immunogold staining to reveal that some bNAbs form large aggregates of virions at the surface of infected cells. This activity correlates with the capacity of bNAbs to bind to Env at the cell surface and to neutralize cell-free viral particles. We further show that antibody bivalency is required for viral retention, and that aggregated virions are neutralized. We have thus identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells.

22 July 2021 in Journal of Antimicrobial Chemotherapy
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Journal Article
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MTMarc-Florent Tassi
Marc-Florent Tassi
ELEmeline Laurent
Emeline Laurent
GGGuillaume Gras
Guillaume Gras
FLFlorence Lot
Florence Lot
FBFrancis Barin
Francis Barin
LGLeslie Grammatico-Guillon
Leslie Grammatico-Guillon
Background: Clinical trials have demonstrated that oral pre-exposure prophylaxis (PrEP) has high efficacy in preventing HIV transmission. In many countries, HIV testing is recommended prior to PrEP initiation, 1 month after and quarterly thereafter. We assessed the uptake of HIV testing and estimated the incidence of HIV infections after oral PrEP initiation, by using the French national health database (SNDS). Methods: A historic cohort study included every adult person who started oral PrEP between 1 January 2016 and 30 June 2018 in France. HIV infection was tracked in the follow-up, from first PrEP dispensation up to 31 December 2018. Factors associated with adherence to HIV testing in PrEP follow-up were analysed using a generalized linear mixed model. Results: PrEP users (9893) were followed for a median duration of 551 days (IQR 350–769). The first HIV test, 1 month after PrEP initiation, was performed by 64% of users. For subsequent tests, this rate exceeded 81% and remained stable over time. HIV testing was lower among PrEP users without prescription refill (OR 0.15; 99% CI 0.12–0.20), but higher if the last prescription was made by a hospital practitioner (OR 2.03; 99% CI 1.69–2.45). Twenty-nine HIV infections were identified, leading to an incidence of 0.19 cases per 100 person-years (99% CI 0.12–0.30). Conclusions: We confirmed good adherence to HIV testing and efficacy of PrEP in users, which should help in decreasing HIV incidence in France. This study also revealed that SNDS could be a powerful automated tool for the epidemiological monitoring of PrEP users.

25 July 2019 in Vaccines
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Journal Article
Open access
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KSKarl Stefic
Karl Stefic
MBMélanie Bouvin-Pley
Mélanie Bouvin-Pley
MBMartine Braibant
Martine Braibant
FBFrancis Barin
Francis Barin
The HIV-1 pandemic remains a major burden on global public health and a vaccine to prevent HIV-1 infection is highly desirable but has not yet been developed. Among the many roadblocks to achieve this goal, the high antigenic diversity of the HIV-1 envelope protein (Env) is one of the most important and challenging to overcome. The recent development of broadly neutralizing antibodies has considerably improved our knowledge on Env structure and its interplay with neutralizing antibodies. This review aims at highlighting how the genetic diversity of HIV-1 thwarts current, and possibly future, vaccine developments. We will focus on the impact of HIV-1 Env diversification on the sensitivity to neutralizing antibodies and the repercussions of this continuous process at a population level.