101 results on '"Braibant M"'
Search Results
2. Cross-group neutralization of HIV-1 and evidence for conservation of the PG9/PG16 epitopes within divergent groups of HIV-1
- Author
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Braibant M, Gong E, Plantier J, Simon F, and Barin F
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
- View/download PDF
3. The breadth of maternal HIV-1 specific neutralizing antibodies is not associated with a lower risk of mother-to-infant transmission
- Author
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Chaillon A, Wack T, Braibant M, Mandelbrot L, Blanche S, Warszawski J, and Barin F
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2012
- Full Text
- View/download PDF
4. P04-17. The N-glycosylation sites N295, N332 and N392 of gp120 are necessary but not sufficient for HIV-1 to be neutralized by 2G12
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Barin F, Autran B, Braibant M, and Chaillon A
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
5. A26 Probing the compartmentalization of HIV-1 in the central nervous system through its neutralization properties
- Author
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Stefic, K, Chaillon, A, Bouvin-Pley, M, Moreau, A, Braibant, M, Bastides, F, Gras, G, Bernard, L, and Barin, F
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Evolutionary Biology ,Microbiology - Published
- 2018
6. Long-term Physicochemical Stability of Concentrated Solutions of Sodium Valproate in Polypropylene Syringes for Administration in the Intensive Care Unit
- Author
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Lardinois, Benjamin, Baltzis, A, Braibant, M, Soumoy, Laura, Jamart, Jacques, BIHIN, Benoît, Hecq, Jean-Daniel, Galanti, Laurence, UCL - (MGD) Unité de support scientifique, UCL - (MGD) Laboratoire de biologie clinique, UCL - (MGD) Département de pharmacie, and UCL - SSS/IREC/MONT - Pôle Mont Godinne
- Subjects
Intensive Care Units ,Drug Storage ,Syringes ,Valproic Acid ,Polypropylenes ,Chromatography, High Pressure Liquid - Abstract
In some situations, drug solutions in higher concentrations are used in intensive care units. The objective of this study was to evaluate the physicochemical stability of concentrated solutions of valproate sodium in polypropylene syringes during 30 days at 5°C ± 3°C. Five syringes of 40 mL containing 20 mg/mL of sodium valproate in 0.9% sodium chloride were prepared and stored at 5°C ± 3°C during 30 days. Immediately after preparation and periodically during the storage, valproate concentrations were measured by high-performance liquid chromatography. Spectrophotometric absorbance at different wavelengths, pH measurement, and microscopic observations were also performed. All solutions were physically stable during the study period storage at 5°C ± 3°C. No color change, turbidity, precipitation, or opacity at visual observation was noticed. No significant pH variations or optic densities were observed. No crystals were seen by microscopic analysis. Concentrations of valproate remained stable during the period of storage. Solutions of sodium valproate 20 mg/mL in syringes of 0.9% sodium chloride were physically and chemically stable for at least 30 days when stored in syringes at 5°C ± 3°C. These solutions may be prepared in advance by a centralized intravenous additive service.
- Published
- 2019
7. Antimycobacterial activity of synthetic pamamycins
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Lefèvre, P., Peirs, P., Braibant, M., Fauville-Dufaux, M., Vanhoof, R., Huygen, K., Wang, X.-M., Pogell, B., Wang, Y., Fischer, P., Metz, P., and Content, J.
- Published
- 2004
8. Effect of amino acid substitutions within the V3 region of HIV-1 CRF01_AE on interaction with CCR5-coreceptor
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Hongjaisee, S., Braibant, M., Barin, F., Ngo-Giang-Huong, Nicole, Sirirungsi, W., and Samleerat, T.
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coreceptor usage ,V3 ,viruses ,HIV-1 ,virus diseases ,CRF01_AE ,CCR5 - Abstract
Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well characterized. We generated V3 mutants using polymerase chain reaction (PCR)-based site-directed mutagenesis of HIV-1 CRF01_AE R5-env plasmids at specific positions. Mutant viruses were produced by env-pseudotyped virus assay, tested for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was assessed with luciferase activity measurement. All viruses, harboring either single or double mutations, used the CCR5 coreceptor. However, those containing a single substitution at positions 7, 11, 18, and 32 and those with mutations at positions 5/32 and 18/32 had reduced infectivity. Only virus with arginine substitution at position 11 seemed to be involved in CXCR4 coreceptor usage. Our results suggest that some V3 positions may be necessary for the binding to coreceptor, but not for the switch of coreceptor usage.
- Published
- 2017
9. 3PC-028 Stability of concentrated solutions of salbutamol hydrochloride in syringes for administration in the intensive care unit
- Author
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Hecq, JD, primary, Lardinois, B, additional, Braibant, M, additional, Baltzys, A, additional, Bihin, B, additional, Jamart, J, additional, Soumoy, L, additional, and Galanti, L, additional
- Published
- 2018
- Full Text
- View/download PDF
10. 4CPS-230 Prospective study to explore the impact of a clinical pharmacist in a cardiac surgical population or after acute coronary syndrome
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Braibant, M, primary, Larock, AS, additional, Dive, A, additional, Horlait, G, additional, Bulpa, P, additional, Michaux, I, additional, Hecq, JD, additional, Krug, B, additional, and Spinewine, A, additional
- Published
- 2018
- Full Text
- View/download PDF
11. Structure of the Mycobacterium tuberculosis antigen 88, a protein related to the Escherichia coli PstA periplasmic phosphate permease subunit
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Braibant M, De Wit L, Peirs P, Kalai M, Ooms J, Drowart A, Kris Huygen, and Content J
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Protein subunit ,Molecular Sequence Data ,Immunology ,Biology ,medicine.disease_cause ,Microbiology ,Bacterial Proteins ,medicine ,Phosphate Transport Proteins ,Amino Acid Sequence ,Cloning, Molecular ,Phosphate permease ,Escherichia coli ,Antigens, Bacterial ,Base Sequence ,Membrane transport protein ,Permease ,Escherichia coli Proteins ,Antibodies, Monoclonal ,Membrane Transport Proteins ,DNA ,Mycobacterium tuberculosis ,Periplasmic space ,Molecular biology ,Transmembrane protein ,Blotting, Southern ,Transmembrane domain ,Infectious Diseases ,Biochemistry ,biology.protein ,ATP-Binding Cassette Transporters ,Parasitology ,Carrier Proteins ,Research Article - Abstract
We report the cloning and sequencing of the gene coding for antigen 88 from Mycobacterium tuberculosis by using monoclonal antibodies to screen an expression library in lambda gt11. The gene encodes a 403-amino-acid-residue protein with a calculated molecular mass of 43,790 Da which contains seven putative transmembrane alpha-helical domains and presents a significant homology to the PstA protein of Escherichia coli. In its N-terminal region, it contains a 61-amino-acid region highly homologous to the fifth transmembrane helix of E. coli PstC. PstA and PstC are the two hydrophobic subunits of an E. coli periplasmic phosphate permease. Since the phosphate-binding subunit of this putative permease in M. tuberculosis has previously been characterized, i.e., the 38-kDa mycobacterial protein (also called protein antigen b, Ag 5, and Ag 78) homologous to PstS of E. coli, it seems likely that functional permeases analogous to the periplasmic permeases of gram-negative bacteria also exist in mycobacteria.
- Published
- 1994
12. Human Immunodeficiency Virus Type 1 variants issued from mother-child pairs display a wide spectrum of biological properties
- Author
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Thenin, S., Braibant, M., Samleerat, T., Ngo-Giang-Huong, Nicole, Jourdain, Gonzague, Lallemant, Marc, and Barin, F.
- Published
- 2011
13. Drift of the HIV-1 Envelope Glycoprotein gp120 toward Increased Neutralization Resistance over the Course of the Epidemic: a Comprehensive Study Using the Most Potent and Broadly Neutralizing Monoclonal Antibodies
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Bouvin-Pley, M., primary, Morgand, M., additional, Meyer, L., additional, Goujard, C., additional, Moreau, A., additional, Mouquet, H., additional, Nussenzweig, M., additional, Pace, C., additional, Ho, D., additional, Bjorkman, P. J., additional, Baty, D., additional, Chames, P., additional, Pancera, M., additional, Kwong, P. D., additional, Poignard, P., additional, Barin, F., additional, and Braibant, M., additional
- Published
- 2014
- Full Text
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14. Characteristics of HIV type 1 (HIV-1) glycoprotein 120 env sequences in mother-infant pairs infected with HIV-1 subtype CRF01_AE
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Samleerat, T., Braibant, M., Jourdain, Gonzague, Moreau, A., Ngo-Giang-Huong, Nicole, Leechanachai, P., Hemvuttiphan, J., Hinjiranandana, T., Changchit, T., Warachit, B., Suraseranivong, V., Lallemant, Marc, and Barin, F.
- Abstract
We analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_ AE clade. A total of 353 sequences covering almost the entire glycoprotein (gp) 120 region were available for analysis. We found that, even if the virus population in the mother was complex, only viruses of a restricted subset were transmitted to her infant, independently of whether transmission occurred in utero or during the intrapartum period. We did not find that shorter gp120 regions or fewer potential N- glycosylation sites(PNGS) were characteristic of viruses transmitted from mother to infant. However, our data suggest that a limited number of PNGS that seem to be conserved in all variants in infants but are not uniformly present in variants in mothers may confer an advantage for transmission of the virus, thereby highlighting the potentially important role of the " glycan shield." This finding was particularly significant for the PNGS at positions N301 and N384.
- Published
- 2008
15. Structural and functional study of Salmonella enterica serovar Typhimurium DT104 floR, an efflux pump belonging to the major facilitator superfamily
- Author
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Braibant, M., Chaslus-Dancla, E., Cloeckaert, Axel, Station de Pathologie aviaire et parasitologie [Nouzilly] (PAP), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,ComputingMilieux_MISCELLANEOUS - Abstract
National audience
- Published
- 2003
16. Immunogenicity and protective efficacy of tuberculosis DNA vaccines encoding putative phosphate transport receptors
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Tanghe A, Lefèvre P, Denis O, D'Souza S, Braibant M, Lozes E, Singh M, Montgomery D, Content J, and Kris Huygen
- Subjects
Antigens, Bacterial ,Escherichia coli Proteins ,Immunology ,Mycobacterium tuberculosis ,Cross Reactions ,Phosphate-Binding Proteins ,Antibodies, Bacterial ,Mycobacterium ,Phosphates ,Mice, Inbred C57BL ,Mice ,Bacterial Proteins ,Periplasmic Binding Proteins ,Bacterial Vaccines ,Vaccines, DNA ,Immunology and Allergy ,Animals ,Interleukin-2 ,Tuberculosis ,ATP-Binding Cassette Transporters ,Female ,Lung ,Spleen ,Plasmids - Abstract
Using culture filtrate Ag-specific mAbs generated from mycobacteria-infected H-2b haplotype mice, we have previously identified three genes in the Mycobacterium tuberculosis genome, encoding proteins homologous to the periplasmic ATP-binding cassette phosphate-binding receptor PstS of the phosphate-specific transport system of E. coli. To define the potential vaccinal properties of these phosphate-binding proteins, female C57BL/6 mice were injected i.m. with plasmid DNA encoding PstS-1, PstS-2, or PstS-3 proteins from M. tuberculosis and immunogenicity and protective efficacy against i.v. challenge with M. tuberculosis H37Rv was analyzed. Significant levels of highly Ag-specific Abs and Th1-type cytokines IL-2 and IFN-γ could be detected following vaccination with each of the three genes. However, only mice vaccinated with PstS-3 DNA demonstrated significant and sustained reduction in bacterial CFU numbers in spleen and lungs for 3 mo after M. tuberculosis challenge, as compared with CFU counts in mice vaccinated with control DNA. Vaccination with PstS-2 DNA induced a modest reduction in CFU counts in spleen only, whereas vaccination with PstS-1 DNA was completely ineffective in reducing bacterial multiplication. In conclusion, our results indicate that DNA vaccination is a powerful and easy method for comparative screening of potentially protective Ags from M. tuberculosis and that the PstS-3 protein is a promising new subunit vaccine candidate.
- Published
- 1999
17. The Breadth and Titer of Maternal HIV-1-Specific Heterologous Neutralizing Antibodies Are Not Associated with a Lower Rate of Mother-to-Child Transmission of HIV-1
- Author
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Chaillon, A., primary, Wack, T., additional, Braibant, M., additional, Mandelbrot, L., additional, Blanche, S., additional, Warszawski, J., additional, and Barin, F., additional
- Published
- 2012
- Full Text
- View/download PDF
18. P04-17. The N-glycosylation sites N295, N332 and N392 of gp120 are necessary but not sufficient for HIV-1 to be neutralized by 2G12
- Author
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Chaillon, A, primary, Braibant, M, additional, Autran, B, additional, and Barin, F, additional
- Published
- 2009
- Full Text
- View/download PDF
19. Anticorps anticardiolipines, réplication virale, anticorps neutralisants et activation immune chez les patients VIH asymptomatiques à long terme
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Martinez, V., primary, Diemert, M.-C., additional, Braibant, M., additional, Potard, V., additional, Costagliola, D., additional, Charuel, J.-L., additional, Barin, F., additional, Caumes, E., additional, Clauvel, J.-P., additional, Musset, L., additional, and Autran, B., additional
- Published
- 2009
- Full Text
- View/download PDF
20. N-03 Anticorps anticardiolipines, réplication virale, anticorps neutralisants et activation immune chez les patients VIH asymptomatiques à long terme
- Author
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Martinez, V., primary, Diemert, M.C., additional, Braibant, M., additional, Potard, V., additional, Costagliola, D., additional, and Charuel, J.L., additional
- Published
- 2008
- Full Text
- View/download PDF
21. Erratum to “The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis” [FEMS Microbiol. Rev. 24 (2000) 449–467]
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Braibant, M, primary
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- 2002
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22. Stability of Concentrated Solution of Vancomycin Hydrochloride in Syringes for Intensive Care Units
- Author
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Godet Marie, Simar Joanna, Closset Mélanie, Hecq Jean-Daniel, Braibant Maximilien, Soumoy Laura, Gillet Patricia, Jamart Jacques, Bihin Benoît, and Galanti Laurence
- Subjects
vancomycin infusions ,concentrated solutions ,high performance liquid chromatography ,physicochemical stability ,syringe ,intensive care units ,Therapeutics. Pharmacology ,RM1-950 ,Pharmaceutical industry ,HD9665-9675 - Abstract
Vancomycin is increasingly administrated by continuous infusion. But the treatment of patient in intensive care need restricted volume to prevent fluid overload. The aim of the study was to evaluate the physical and chemical stability of solutions of a high concentration of vancomycin hydrochloride in 5 % glucose or 0.9 % NaCl.
- Published
- 2018
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- View/download PDF
23. Three different putative phosphate transport receptors are encoded by the Mycobacterium tuberculosis genome and are present at the surface of Mycobacterium bovis BCG
- Author
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Lefèvre, P, primary, Braibant, M, additional, de Wit, L, additional, Kalai, M, additional, Röeper, D, additional, Grötzinger, J, additional, Delville, J P, additional, Peirs, P, additional, Ooms, J, additional, Huygen, K, additional, and Content, J, additional
- Published
- 1997
- Full Text
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24. Characteristics of HIV type 1 (HIV-1) glycoprotein 120 env sequences in mother-infant pairs infected with HIV-1 subtype CRF01 AE.
- Author
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Samleerat T, Braibant M, Jourdain G, Moreau A, Ngo-Giang-Huong N, Leechanachai P, Hemvuttiphan J, Hinjiranandana T, Changchit T, Warachit B, Suraseranivong V, Lallemant M, and Barin F
- Abstract
We analyzed the characteristics of the envelope genes of human immunodeficiency virus type 1 in 17 mother-infant pairs infected with variants of the CRF01_AE clade. A total of 353 sequences covering almost the entire glycoprotein (gp) 120 region were available for analysis. We found that, even if the virus population in the mother was complex, only viruses of a restricted subset were transmitted to her infant, independently of whether transmission occurred in utero or during the intrapartum period. We did not find that shorter gp120 regions or fewer potential N-glycosylation sites (PNGS) were characteristic of viruses transmitted from mother to infant. However, our data suggest that a limited number of PNGS that seem to be conserved in all variants in infants but are not uniformly present in variants in mothers may confer an advantage for transmission of the virus, thereby highlighting the potentially important role of the 'glycan shield.' This finding was particularly significant for the PNGS at positions N301 and N384. Copyright © 2008 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
25. 3PC-028 Stability of concentrated solutions of salbutamol hydrochloride in syringes for administration in the intensive care unit
- Author
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Hecq, JD, Lardinois, B, Braibant, M, Baltzys, A, Bihin, B, Jamart, J, Soumoy, L, and Galanti, L
- Abstract
BackgroundIn order to avoid fluid overload, the use of more concentrated drug solutions in intensive care units is common.PurposeQuantifying the physicochemical stability of concentrated solution of salbutamol in polypropylene syringe during 30 days at 5°C±3°C with protection from light.Material and methodsFive syringes of 50 ml, containing 0.060 mg/ml of salbutamol in 0.9% NaCl were prepared and stored at 5°C±3°C with protection from light during 30 days. Immediately after preparation and periodically during the storage, salbutamol concentrations were measured by an ultra performance liquid chromatography (UPLC). Spectrophotometric absorbance at different wavelengths, pH measurement, and visual and microscopic observations were also performed.ResultsAll solutions were physicochemically stable during the whole period storage at 5°C±3°C: no colour change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable, as the lower limit of the 95% unilateral confidence interval on the mean remained above 90% of the initial concentration for at least 30 days.ConclusionSolutions of salbutamol 0.060 mg/ml in syringe of 0.9% NaCl are physically and chemically stable for at least 30 days when stored in syringes at 5°C±3°C with protection from light, and may be prepared in advance by a Centralised IntraVenous Admixture Service (CIVA).Reference and/or Acknowledgements1. Closset M, Hecq JD, Soumoy L, Simar J, Gonzalez E, Charlet L, Declave C, Gillet P, Galanti L. Physical stability of highly concentrated injectable drugs solutions used in intensive care units. Ann Pharm Fr201713 Feb;S0003–4509(16):30055–4. doi: 10. 1016/j. pharma. 2016. 12. 004No conflict of interest
- Published
- 2018
- Full Text
- View/download PDF
26. Vocation agricole de la France
- Author
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G., G., primary and Braibant, M.-H., additional
- Published
- 1960
- Full Text
- View/download PDF
27. Maternal neutralizing antibodies against a CRF01_AE primary isolate are associated with a low rate of intrapartum HIV-1 transmission in Thailand
- Author
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Moreau Alain, Ngo-Giang-Huong Nicole, Jourdain Gonzague, Samleerat Tanawan, Thenin Suzie, Leechanachai Pranee, Lallemand Marc, Barin Françis, and Braibant Martine
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2009
- Full Text
- View/download PDF
28. Characteristics of HIV-1 gp120 env sequences in mother-child pairs infected with HIV-1 subtype CRF01_AE
- Author
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Hemvuttiphan Jittapol, Hinjiranandana Temsiri, Leechanachai Pranee, Ngo-Giang-Huong Nicole, Moreau Alain, Jourdain Gonzague, Braibant Martine, Samleerat Tanawan, Changchit Tikamporn, Warachit Boonyarat, Suraseranivong Veera, Lallemant Marc, and Barin Francis
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2008
- Full Text
- View/download PDF
29. 4CPS-230 Prospective study to explore the impact of a clinical pharmacist in a cardiac surgical population or after acute coronary syndrome
- Author
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Braibant, M, Larock, AS, Dive, A, Horlait, G, Bulpa, P, Michaux, I, Hecq, JD, Krug, B, and Spinewine, A
- Abstract
BackgroundPatients in the intensive care unit (ICU) are at risk of medication errors (polypharmacy, critical nature of their illnesses and use of high-risk drugs). Collaboration with a clinical pharmacist can be helpful in minimising these risks. In order to develop and sustain clinical pharmacy activity in the ICU at our hospital, formal evaluation of the potential benefit was required.PurposeTo describe the characteristics of interventions performed by an ICU clinical pharmacist, including their clinical relevance and likelihood of preventing adverse drug events (ADEs), as well as carrying out a cost analysis on a subgroup of critical interventions.Material and methodsA prospective interventional study was conducted in the cardiac and cardio-surgical ICU of a university teaching hospital. The clinical pharmacist provided pharmaceutical care to cardiovascular surgical and acute coronary syndrome ICU patients over a 9 week period.All clinical pharmacy interventions (CPIs) were recorded and evaluated by two independent evaluators for clinical relevance and likelihood of preventing ADEs. The CPIs were categorised in a risk classification system adapted from the Society of Hospital Pharmacists of Australia.For the cost analysis, we relied on German adverse drug events micro-costing data by Rottenkolber et al.ResultsA total of 230 CPIs were performed in 58 patients. The acceptance rate was 85.5%. The medication classes most frequently involved were: blood and coagulation (16.9%), cardiovascular system (14.8%), pain and fever drugs (14.8%). Sixty-six (33.8%) interventions were considered high/extreme risk, and anticoagulants and antiplatelet agents alone accounted for 25.8% of those.The cut-off to cover the salary of the clinical pharmacist could be reached, if 24 severe adverse events on anticoagulants and antiplatelet agents were avoided per 7 weeks.Two-thirds of all CPIs required the presence of the pharmacist in the unit. Analysis of the medical record (45.1%) and contact with a primary care provider (46.7%) were proportionally the sources of information most often used in the case of high/extreme CPIs.ConclusionThis study provides data that supports the expansion of clinical pharmacy services to cardiovascular surgical patients in the ICU.Reference and/or Acknowledgements1. Rottenkolber D, et al. Costs of adverse drug events in German hospitals – a microcosting study. Value Health2012Sep–Oct;15(6):868–875.No conflict of interest
- Published
- 2018
- Full Text
- View/download PDF
30. Role of Viral Envelope Proteins in Determining Susceptibility of Viruses to IFITM Proteins.
- Author
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Marceau T and Braibant M
- Subjects
- Interferons pharmacology, Membrane Proteins genetics, Membrane Proteins metabolism, Cell Membrane metabolism, Virus Internalization, Viral Envelope Proteins, HIV-1 physiology
- Abstract
Interferon-induced transmembrane proteins (IFITMs) are a family of proteins which inhibit infections of various enveloped viruses. While their general mechanism of inhibition seems to be non-specific, involving the tightening of membrane structures to prevent fusion between the viral envelope and cell membrane, numerous studies have underscored the importance of viral envelope proteins in determining the susceptibility of viruses to IFITMs. Mutations in envelope proteins may lead to viral escape from direct interaction with IFITM proteins or result in indirect resistance by modifying the viral entry pathway, allowing the virus to modulate its exposure to IFITMs. In a broader context, the nature of viral envelope proteins and their interaction with IFITMs can play a crucial role in the context of adaptive immunity, leading to viral envelope proteins that are more susceptible to antibody neutralization. The precise mechanisms underlying these observations remain unclear, and further studies in this field could contribute to a better understanding of how IFITMs control viral infections.
- Published
- 2024
- Full Text
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31. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller.
- Author
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Molinos-Albert LM, Baquero E, Bouvin-Pley M, Lorin V, Charre C, Planchais C, Dimitrov JD, Monceaux V, Vos M, Hocqueloux L, Berger JL, Seaman MS, Braibant M, Avettand-Fenoël V, Sáez-Cirión A, and Mouquet H
- Subjects
- Humans, Broadly Neutralizing Antibodies, HIV Antibodies, Antibodies, Neutralizing, Viremia, Antigens, Viral, Polysaccharides, env Gene Products, Human Immunodeficiency Virus, HIV-1, HIV Infections drug therapy
- Abstract
HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the
324 GDIR327 V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
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32. Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller.
- Author
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Lorin V, Fernández I, Masse-Ranson G, Bouvin-Pley M, Molinos-Albert LM, Planchais C, Hieu T, Péhau-Arnaudet G, Hrebík D, Girelli-Zubani G, Fiquet O, Guivel-Benhassine F, Sanders RW, Walker BD, Schwartz O, Scheid JF, Dimitrov JD, Plevka P, Braibant M, Seaman MS, Bontems F, Di Santo JP, Rey FA, and Mouquet H
- Subjects
- Animals, Antibodies, Neutralizing, Broadly Neutralizing Antibodies, Elite Controllers, Epitopes, HIV Antibodies, Humans, Immunoglobulin A, Immunoglobulin G, Mice, Polysaccharides, env Gene Products, Human Immunodeficiency Virus, HIV Infections, HIV-1
- Abstract
Decrypting the B cell ontogeny of HIV-1 broadly neutralizing antibodies (bNAbs) is paramount for vaccine design. Here, we characterized IgA and IgG bNAbs of three distinct B cell lineages in a viremic controller, two of which comprised only IgG+ or IgA+ blood memory B cells; the third combined both IgG and IgA clonal variants. 7-269 bNAb in the IgA-only lineage displayed the highest neutralizing capacity despite limited somatic mutation, and delayed viral rebound in humanized mice. bNAbs in all three lineages targeted the N332 glycan supersite. The 2.8-Å resolution cryo-EM structure of 7-269-BG505 SOSIP.664 complex showed a similar pose as 2G12, on an epitope mainly composed of sugar residues comprising the N332 and N295 glycans. Binding and cryo-EM structural analyses showed that antibodies from the two other lineages interact mostly with glycans N332 and N386. Hence, multiple B cell lineages of IgG and IgA bNAbs focused on a unique HIV-1 site of vulnerability can codevelop in HIV-1 viremic controllers., Competing Interests: Disclosures: F.A. Rey is a board member of EureKARE and MELETIUS Therapeutics. No other disclosures were reported., (© 2022 Lorin et al.)
- Published
- 2022
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33. Escape of HIV-1 envelope glycoprotein from the restriction of infection by IFITM3.
- Author
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Drouin A, Migraine J, Durand MA, Moreau A, Burlaud-Gaillard J, Beretta M, Roingeard P, Bouvin-Pley M, and Braibant M
- Abstract
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that reduces HIV-1 infectivity by an incompletely understood mechanism. We show here that viruses differing only in the envelope glycoprotein (Env) expressed on their surface have different sensitivities to IFITM3. Measurements of the sensitivity of viruses to neutralizing antibodies showed that IFITM3 increased the sensitivity of IFITM3-sensitive viruses to PG16, which targets the V1V2 loop, suggesting that IFITM3 promotes exposure of the PG16 epitope of IFITM3-sensitive viruses. Exchanges of V1V2 loops between the Env proteins of sensitive and resistant viruses revealed that V1V2 and V3 act together to modulate viral sensitivity to IFITM3. Co-immunoprecipitation experiments showed that IFITM3 interacted with both the precursor (gp160) and cleaved (gp120) forms of Env from IFITM3-sensitive viruses, but only with the precursor (gp160) form of Env from IFITM3-resistant viruses. This finding suggests that the interaction between the Env of resistant viruses and IFITM3 was inhibited once Env had been processed in the Golgi apparatus. This hypothesis was supported by immunofluorescence experiments, which showed a strong colocalization of IFITM3 with the Env of sensitive viruses, but only weak colocalization with the Env of resistant viruses on the plasma membrane of virus-producing cells. Together, these results indicate that IFITM3 interacts with Env, inducing conformational changes that may decrease viral infectivity. This antiviral action is, nevertheless, modulated by the nature of the Env, in particular its V1V2 and V3 loops, which after maturation may be able to escape this interaction. IMPORTANCE Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that reduces HIV-1 infectivity by an incompletely understood mechanism. This study aimed to elucidate the role of the HIV-1 envelope glycoprotein (Env) in determining viral susceptibility to IFITM3. We found that viruses differing only in Env expressed on their surface had different sensitivities to IFITM3. By comparing the Env proteins of viruses that were highly sensitive or resistant to IFITM3, we obtained new insight in the mechanisms by which HIV-1 escapes this protein. We showed that IFITM3 interacts with the Env protein of sensitive viruses in virion-producing cells, inducing conformational changes that may decrease viral infectivity. However, this antiviral action is modulated by the nature of Env, particularly the V1V2 and V3 loops, which may be able to escape this interaction after processing in the Golgi., (Copyright © 2020 American Society for Microbiology.)
- Published
- 2021
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34. A Comparison of Cell Activation, Exhaustion, and Expression of HIV Coreceptors and Restriction Factors in HIV-1- and HIV-2-Infected Nonprogressors.
- Author
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Diallo MS, Samri A, Charpentier C, Bertine M, Cheynier R, Thiébaut R, Matheron S, Collin F, Braibant M, Candotti D, Brun-Vézinet F, and Autran B
- Subjects
- Antiviral Restriction Factors, CD4-Positive T-Lymphocytes, HIV Long-Term Survivors, HIV-2, Humans, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, HIV Infections, HIV-1
- Abstract
Human immunodeficiency viruses induce rare attenuated diseases due either to HIV-1 in the exceptional long-term nonprogressors (LTNPs) or to HIV-2 in West Africa. To better understand characteristics of these two disease types we performed a multiplex comparative analysis of cell activation, exhaustion, and expression of coreceptors and restriction factors in CD4 T cells susceptible to harbor those viruses. We analyzed by flow cytometry the expression of HLA-DR, PD1, CCR5, CXCR6, SAMHD1, Blimp-1, and TRIM5α on CD4 T cell subsets from 10 HIV-1
+ LTNPs and 14 HIV-2+ (12 nonprogressors and 2 progressors) of the ANRS CO-15 and CO-5 cohorts, respectively, and 12 HIV- healthy donors (HD). The V3 loop of the HIV-1 envelope from 6 HIV-1+ LTNPs was sequenced to determine the CXCR6-binding capacity. Proportions of HLA-DR+ and PD1+ cells were higher in memory CD4 T subsets from HIV-1 LTNPs compared with HIV-2 and HD. Similar findings were observed for CCR5+ cells although limited to central-memory CD4 T cell (TCM) and follicular helper T cell subsets, whereas all major subsets from HIV-1 LTNPs contained less CXCR6+ cells compared with HIV-2. All six V3 loop sequences from HIV-1 LTNPs contained a proline at position 326. Proportions of SAMHD1+ cells were higher in all resting CD4 T subsets from HIV-1 LTNPs compared with the other groups, whereas Blimp-1+ and Trim5α+ cells did not differ. The CD4 T cell subsets from HIV-1 LTNPs differ from those of HIV-2-infected subjects by higher levels of activation, exhaustion, and SAMHD1 expression that can reflect the distinct patterns of host/virus relationships.- Published
- 2021
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35. Differential utilization of CD4+ by transmitted/founder and chronic envelope glycoproteins in a MSM HIV-1 subtype B transmission cluster.
- Author
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Bouvin-Pley M, Leoz M, Roch E, Moreau A, Migraine J, Bellini N, Blake O, Mammano F, Braibant M, Plantier JC, and Brand D
- Subjects
- Humans, Male, CD4-Positive T-Lymphocytes immunology, Glycoproteins genetics, Glycoproteins immunology, Glycoproteins metabolism, HIV Infections immunology, HIV Infections transmission, HIV Infections virology, HIV-1 genetics, HIV-1 immunology, HIV-1 metabolism, Homosexuality, Male, Viral Envelope Proteins genetics, Viral Envelope Proteins immunology, Viral Envelope Proteins metabolism
- Abstract
Objective: HIV-1 transmission leads to a genetic bottleneck, with one or a few variants of the donor quasispecies establishing an infection in the new host. We aimed to characterize this bottleneck in more detail, by comparing the properties of HIV envelope glycoproteins from acute and chronic infections within the particular context of a male-to-male transmission cluster., Design: We compared the genotypic and phenotypic properties of envelope glycoproteins from viral variants derived from five study participants from the same transmission cluster., Methods: We used single-genome amplification to generate a collection of full-length env sequences. We then constructed pseudotyped viruses expressing selected Env variants from the quasispecies infecting each study participant and compared their infectivities and sensitivities to various entry inhibitors., Results: The genotypic analyses confirmed the genetic bottleneck expected after HIV transmission, with a limited number of variants identified in four study participants during acute infection. However, the transmitted sequences harbored no evident common signature and belonged to various genetic lineages. The phenotypic analyses revealed no difference in infectivity, susceptibility to the CCR5 antagonist maraviroc, the fusion inhibitor enfurvitide or type-I interferon between viruses from participants with acute and chronic infections. The key property distinguishing transmitted viruses was a higher resistance to soluble CD4, correlated with greater sensitivity to occupation of the CD4 receptor by the anti-CD4 antibodies LM52 and SK3., Conclusion: These results suggest that envelope glycoproteins from transmitted/founder viruses bind CD4 less efficiently than those of viruses from chronic infections.
- Published
- 2020
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36. Common evolutionary features of the envelope glycoprotein of HIV-1 in patients belonging to a transmission chain.
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Beretta M, Migraine J, Moreau A, Essat A, Goujard C, Chaix ML, Drouin A, Bouvin-Pley M, Meyer L, Barin F, and Braibant M
- Subjects
- Humans, Male, Monocytes metabolism, Monocytes virology, Evolution, Molecular, HIV Infections virology, HIV-1 metabolism, Viral Envelope Proteins metabolism
- Abstract
The diversity of the HIV-1 envelope glycoproteins (Env) is largely a consequence of the pressure exerted by the adaptive immune response to infection. While it was generally assumed that the neutralizing antibody (NAb) response depended mainly on the infected individual, the concept that virus-related factors could be important in inducing this response has recently emerged. Here, we analyzed the influence of the infecting viral strain in shaping NAb responses in four HIV-1 infected subjects belonging to a transmission chain. We also explored the impact of NAb responses on the functional evolution of the viral quasispecies. The four patients developed a strong autologous neutralizing antibody response that drove viral escape and coincided with a parallel evolution of their infecting quasispecies towards increasing infectious properties, increasing susceptibility to T20 and increasing resistance to both CD4 analogs and V3 loop-directed NAbs. This evolution was associated with identical Env sequence changes at several positions in the V3 loop, the fusion peptide and the HR2 domain of gp41. The common evolutionary pattern of Env in different hosts suggests that the capacity of a given Env to adapt to changing environments may be restricted by functional constraints that limit its evolutionary landscape.
- Published
- 2020
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37. Impact of HIV-1 Diversity on Its Sensitivity to Neutralization.
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Stefic K, Bouvin-Pley M, Braibant M, and Barin F
- Abstract
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.
- Published
- 2019
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38. HIV-1 antibodies in prevention of transmission.
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Barin F and Braibant M
- Subjects
- Animals, HIV Infections immunology, HIV Infections transmission, HIV Infections virology, HIV-1 genetics, Humans, Immunization, Passive, Pre-Exposure Prophylaxis, HIV Antibodies immunology, HIV Infections prevention & control, HIV-1 immunology
- Abstract
Purpose of Review: To present the data that suggest that antibodies to HIV may prevent HIV-1 infection., Recent Findings: Many human monoclonal broadly neutralizing antibodies (bnAbs) have been isolated over the last decade. Numerous experiments of passive immunization in nonhuman primate models have allowed to accumulate strong evidences that bnAbs, opposed to nonneutralizing antibodies, are the best candidates to prevent HIV-1 infection. bnAbs counteract HIV-1 by both blocking the virus at the portal of entry and clearing rapidly viral foci established at distance after dissemination of the virus following infection. Cocktails of bnAbs or modified bi/trispecific antibodies will be necessary to counter the large and evolving antigenic diversity of the HIV-1 species. Two large multicenter phase IIb clinical trials have been initiated. Even if they are not conducted with the most recent and most potent bnAb, the results which are expected in 2022 will inform us on the real potency of bnAbs at preventing HIV-1 acquisition in the real life., Summary: If these trials demonstrate the efficacy of bnAbs, they will open the trail toward new strategies for preexposure prophylaxis, eventually postexposure prophylaxis and prevention of mother-to-child transmission.
- Published
- 2019
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39. Evolution of the Envelope Glycoprotein of HIV-1 Clade B toward Higher Infectious Properties over the Course of the Epidemic.
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Bouvin-Pley M, Beretta M, Moreau A, Roch E, Essat A, Goujard C, Chaix ML, Moiré N, Martin L, Meyer L, Barin F, and Braibant M
- Subjects
- Antibodies, Neutralizing immunology, Cell Line, Epidemics, HEK293 Cells, HIV Antibodies immunology, HIV Envelope Protein gp120 immunology, HIV Envelope Protein gp120 metabolism, HIV Infections immunology, HIV-1 immunology, Humans, Male, Neutralization Tests methods, Receptors, CCR5 metabolism, Virus Internalization, env Gene Products, Human Immunodeficiency Virus immunology, HIV Infections virology, HIV-1 metabolism, HIV-1 pathogenicity, env Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
We showed previously that during the HIV/AIDS epidemic, the envelope glycoprotein (Env) of HIV-1, and in particular, the gp120 subunit, evolved toward an increased resistance to neutralizing antibodies at a population level. Here, we considered whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. We tested the infectivity of a panel of Env-pseudotyped viruses derived from patients infected by subtype B viruses at three periods of the epidemic (1987 to 1991, 1996 to 2000, and 2006 to 2010). Pseudotyped viruses harboring Env from patients infected during the most recent period were approximately 10-fold more infectious in cell culture than those from patients infected at the beginning of the epidemic. This was associated with faster viral entry kinetics: contemporary viruses entered target cells approximately twice as fast as historical viruses. Contemporary viruses were also twice as resistant as historical viruses to the fusion inhibitor enfuvirtide. Resistance to enfuvirtide correlated with a resistance to CCR5 antagonists, suggesting that contemporary viruses expanded their CCR5 usage efficiency. Viruses were equally captured by DC-SIGN, but after binding to DC-SIGN, contemporary viruses infected target cells more efficiently than historical viruses. Thus, we report evidence that the infectious properties of the envelope glycoprotein of HIV-1 increased during the course of the epidemic. It is plausible that these changes affected viral fitness during the transmission process and might have contributed to an increasing virulence of HIV-1. IMPORTANCE Following primary infection by HIV-1, neutralizing antibodies (NAbs) exert selective pressure on the HIV-1 envelope glycoprotein (Env), driving the evolution of the viral population. Previous studies suggested that, as a consequence, Env has evolved at the HIV species level since the start of the epidemic so as to display greater resistance to NAbs. Here, we investigated whether the antigenic evolution of the HIV-1 Env is associated with modifications of its functional properties, focusing on cell entry efficacy and interactions with the receptor and coreceptors. Our data provide evidence that the infectious properties of the HIV-1 Env increased during the course of the epidemic. These changes may have contributed to increasing virulence of HIV-1 and an optimization of transmission between individuals., (Copyright © 2019 American Society for Microbiology.)
- Published
- 2019
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40. Sensitivity to Broadly Neutralizing Antibodies of Recently Transmitted HIV-1 Clade CRF02_AG Viruses with a Focus on Evolution over Time.
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Stefic K, Bouvin-Pley M, Essat A, Visdeloup C, Moreau A, Goujard C, Chaix ML, Braibant M, Meyer L, and Barin F
- Subjects
- Adult, Evolution, Molecular, Female, HIV Antibodies pharmacology, HIV-1 classification, HIV-1 genetics, Humans, Immunization, Passive, Male, Middle Aged, Neutralization Tests, Young Adult, env Gene Products, Human Immunodeficiency Virus genetics, Antibodies, Neutralizing pharmacology, HIV Infections virology, HIV-1 drug effects, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Broadly neutralizing antibodies (bnAbs) are promising agents for prevention and/or treatment of HIV-1 infection. However, the diversity among HIV-1 envelope (Env) glycoproteins impacts bnAb potency and breadth. Neutralization data on the CRF02_AG clade are scarce although it is highly prevalent in West Africa and Europe. We assessed the sensitivity to bnAbs of a panel of 33 early transmitted CRF02_AG viruses over a 15-year period of the French epidemic (1997 to 2012). Env pseudotyped CRF02_AG viruses were best neutralized by the CD4 binding site (CD4bs)-directed bnAbs (VRC01, 3BNC117, NIH45-46
G54W , and N6) and the gp41 membrane-proximal external region (MPER)-directed bnAb 10E8 in terms of both potency and breadth. We observed a higher resistance to bnAbs targeting the V1V2-glycan region (PG9 and PGT145) and the V3-glycan region (PGT121 and 10-1074). Combinations were required to achieve full coverage across this subtype. We observed increased resistance to bnAbs targeting the CD4bs linked to the diversification of CRF02_AG Env over the course of the epidemic, a phenomenon which was previously described for subtypes B and C. These data on the sensitivity to bnAbs of CRF02_AG viruses, including only recently transmitted viruses, will inform future passive immunization studies. Considering the drift of the HIV-1 species toward higher resistance to neutralizing antibodies, it appears necessary to keep updating existing panels for evaluation of future vaccine and passive immunization studies. IMPORTANCE Major progress occurred during the last decade leading to the isolation of human monoclonal antibodies, termed broadly neutralizing antibodies (bnAbs) due to their capacity to neutralize various strains of HIV-1. Several clinical trials are under way in order to evaluate their efficacy in preventive or therapeutic strategies. However, no single bnAb is active against 100% of strains. It is important to gather data on the sensitivity to neutralizing antibodies of all genotypes, especially those more widespread in regions where the prevalence of HIV-1 infection is high. Here, we assembled a large panel of clade CRF02_AG viruses, the most frequent genotype circulating in West Africa and the second most frequent found in several European countries. We evaluated their sensitivities to bnAbs, including those most advanced in clinical trials, and looked for the best combinations. In addition, we observed a trend toward increased resistance to bnAbs over the course of the epidemic., (Copyright © 2019 American Society for Microbiology.)- Published
- 2019
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41. Phenotypic properties of envelope glycoproteins of transmitted HIV-1 variants from patients belonging to transmission chains.
- Author
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Beretta M, Moreau A, Bouvin-Pley M, Essat A, Goujard C, Chaix ML, Hue S, Meyer L, Barin F, and Braibant M
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV-1 isolation & purification, Humans, Male, Neutralization Tests, Selection, Genetic, Disease Transmission, Infectious, HIV Infections transmission, HIV Infections virology, HIV-1 growth & development, HIV-1 immunology, Virus Internalization, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
Objective: Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses., Design: We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains., Methods: We generated pseudotyped viruses expressing Env variants of the viral quasispecies infecting each patient and compared their sensitivity to neutralization by eight human monoclonal broadly neutralizing antibodies (HuMoNAbs). We also compared their infectious properties by measuring their infectivity and sensitivity to various entry inhibitors., Results: Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity, providing evidence that the transmission bottleneck is mainly nonstochastic. Transmitted viruses were CCR5-tropic, sensitive to MVC, and resistant to soluble forms of CD4, irrespective of the cluster to which they belonged. They were also sensitive to HuMoNAbs that target V3, the CD4-binding site, and the MPER region, suggesting that the loss of these epitopes may compromise their capacity to be transmitted., Conclusion: Our data suggest that the transmission bottleneck is governed by selective forces. How these forces confer an advantage to the transmitted virus has yet to be determined.
- Published
- 2018
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42. Evaluation of the DOAC-Stop® Procedure to Overcome the Effect of DOACs on Several Thrombophilia Screening Tests.
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Favresse J, Lardinois B, Sabor L, Devalet B, Vandepapeliere J, Braibant M, Lessire S, Chatelain B, Jacqmin H, Douxfils J, and Mullier F
- Abstract
The impact of direct oral anticoagulants (DOACs) on laboratory assays used for thrombophilia testing (e.g., antithrombin, protein S, protein C, lupus anticoagulant and activated protein-C resistance) is a well-known issue and may cause false-positive and -negative results. Therefore, the correct interpretation of tests that are performed in patients taking DOACs is mandatory to prevent misclassification and the subsequent clinical consequences. We aimed at evaluating the efficiency of a new and simple procedure (DOAC-Stop®; Haematex Research, Hornsby, Australia) to overcome the effect of all DOACs in real-life settings and to assess the percentage of erroneous results due to the presence of DOACs on thrombophilia screening tests. For this purpose, 135 DOAC-treated patients (38 apixaban, 40 dabigatran, 15 edoxaban, and 42 rivaroxaban) and 20 control patients were enrolled. A significant drop in apixaban, dabigatran, edoxaban, and rivaroxaban plasma concentrations following the DOAC-Stop® treatment was observed (74.8-8.2 ng/mL [ p < 0.0001], 95.9-4.7 ng/mL [ p < 0.0001], 102.1-8.8 ng/mL [ p = 0.001], and 111.3-7.0 ng/mL [ p < 0.0001], respectively). The DOAC-Stop® treatment was mostly effective to overcome the effect of DOACs on PTT-LA, dilute Russell's viper venom time (dRVVT) screen, and dRVVT confirm tests. Using our procedures, false-positive results due to DOACs were observed only with lupus anticoagulant tests (up to 75%) and fell to zero after the DOAC-Stop® procedure, regardless of the DOAC considered. In conclusion, the DOAC-Stop® adsorbent procedure appeared to be an effective and simple way to overcome the interference of DOAC on coagulation tests and should facilitate the interpretation of thrombophilia screening tests in patients taking DOACs.
- Published
- 2018
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43. Effect of Amino Acid Substitutions Within the V3 Region of HIV-1 CRF01_AE on Interaction with CCR5-Coreceptor.
- Author
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Hongjaisee S, Braibant M, Barin F, Ngo-Giang-Huong N, Sirirungsi W, and Samleerat T
- Subjects
- Cell Line, HEK293 Cells, Humans, Mutagenesis, Site-Directed methods, Mutation genetics, Virus Internalization, Amino Acid Substitution genetics, HIV Infections metabolism, HIV Infections virology, HIV-1 genetics, Receptors, CCR5 metabolism, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus metabolism
- Abstract
Specific amino acids within the V3 loop of HIV-1 CRF01_AE envelope glycoprotein that are involved in the interaction with CCR5/CXCR4 coreceptors, are not well characterized. We generated V3 mutants using polymerase chain reaction (PCR)-based site-directed mutagenesis of HIV-1 CRF01_AE R5-env plasmids at specific positions. Mutant viruses were produced by env-pseudotyped virus assay, tested for coreceptor usage using U373.R5 and U373.X4 cells, and viral entry was assessed with luciferase activity measurement. All viruses, harboring either single or double mutations, used the CCR5 coreceptor. However, those containing a single substitution at positions 7, 11, 18, and 32 and those with mutations at positions 5/32 and 18/32 had reduced infectivity. Only virus with arginine substitution at position 11 seemed to be involved in CXCR4 coreceptor usage. Our results suggest that some V3 positions may be necessary for the binding to coreceptor, but not for the switch of coreceptor usage.
- Published
- 2017
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44. Probing the compartmentalization of HIV-1 in the central nervous system through its neutralization properties.
- Author
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Stefic K, Chaillon A, Bouvin-Pley M, Moreau A, Braibant M, Bastides F, Gras G, Bernard L, and Barin F
- Subjects
- HIV Infections blood, HIV Infections cerebrospinal fluid, HIV Infections virology, HIV-1 immunology, Humans, Longitudinal Studies, Phylogeny, Antibodies, Neutralizing immunology, Central Nervous System virology, HIV-1 isolation & purification
- Abstract
Compartmentalization of HIV-1 has been observed in the cerebrospinal fluid (CSF) of patients at different clinical stages. Considering the low permeability of the blood-brain barrier, we wondered if a reduced selective pressure by neutralizing antibodies (NAb) in the central nervous system (CNS) could favor the evolution of NAb-sensitive viruses in this compartment. Single genome amplification (SGA) was used to sequence full-length HIV-1 envelope variants (453 sequences) from paired CSF and blood plasma samples in 9 subjects infected by HIV variants of various clades and suffering from diverse neurologic disorders. Dynamics of viral evolution were evaluated with a bayesian coalescent approach for individuals with longitudinal samples. Pseudotyped viruses expressing envelope glycoproteins variants representative of the quasi-species present in each compartment were generated, and their sensitivity to autologous neutralization, broadly neutralizing antibodies (bNAbs) and entry inhibitors was assessed. Significant compartmentalization of HIV populations between blood and CSF were detected in 5 out of 9 subjects. Some of the previously described genetic determinants for compartmentalization in the CNS were observed regardless of the HIV-1 clade. There was no difference of sensitivity to autologous neutralization between blood- and CSF-variants, even for subjects with compartmentalization, suggesting that selective pressure by autologous NAb is not the main driver of HIV evolution in the CNS. However, we observed major differences of sensitivity to sCD4 or to at least one bNAb targeting either the N160-V1V2 site, the N332-V3 site or the CD4bs, between blood- and CSF-variants in all cases. In particular, HIV-1 variants present in the CSF were more resistant to bNAbs than their blood counterpart in some cases. Considering the possible migration from CSF to blood, the CNS could be a reservoir of bNAb resistant viruses, an observation that should be considered for immunotherapeutic approaches.
- Published
- 2017
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45. Buffering deleterious polymorphisms in highly constrained parts of HIV-1 envelope by flexible regions.
- Author
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Gasser R, Hamoudi M, Pellicciotta M, Zhou Z, Visdeloup C, Colin P, Braibant M, Lagane B, and Negroni M
- Subjects
- Amides pharmacology, Antigenic Variation, CD4 Antigens metabolism, Evolution, Molecular, Genetic Variation, HIV Envelope Protein gp120 chemistry, HIV Envelope Protein gp120 immunology, HIV Fusion Inhibitors pharmacology, HIV-1 immunology, HIV-1 physiology, Humans, Protein Stability, Quaternary Ammonium Compounds pharmacology, Receptors, CCR5 metabolism, Sequence Alignment, Virus Internalization, HIV Envelope Protein gp120 genetics, HIV-1 genetics, Polymorphism, Genetic
- Abstract
Background: Covariation is an essential process that leads to coevolution of parts of proteins and genomes. In organisms subject to strong selective pressure, coevolution is central to keep the balance between the opposite requirements of antigenic variation and retention of functionality. Being the viral component most exposed to the external environment, the HIV-1 glycoprotein gp120 constitutes the main target of the immune response. Accordingly its more external portions are characterised by extensive sequence heterogeneity fostering constant antigenic variation., Results: We report that a single polymorphism, present at the level of the viral population in the conserved internal region C2, was sufficient to totally abolish Env functionality when introduced in an exogenous genetic context. The prominent defect of the non-functional protein is a block occurring after recognition of the co-receptor CCR5, likely due to an interference with the subsequent conformational changes that lead to membrane fusion. We also report that the presence of compensatory polymorphisms at the level of the external and hypervariable region V3 fully restored the functionality of the protein. The functional revertant presents different antigenic profiles and sensitivity to the entry inhibitor TAK 779., Conclusions: Our data suggest that variable regions, besides harbouring intrinsic extensive antigenic diversity, can also contribute to sequence diversification in more structurally constrained parts of the gp120 by buffering the deleterious effect of polymorphisms, further increasing the genetic flexibility of the protein and the antigenic repertoire of the viral population.
- Published
- 2016
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46. V1/V2 Neutralizing Epitope is Conserved in Divergent Non-M Groups of HIV-1.
- Author
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Morgand M, Bouvin-Pley M, Plantier JC, Moreau A, Alessandri E, Simon F, Pace CS, Pancera M, Ho DD, Poignard P, Bjorkman PJ, Mouquet H, Nussenzweig MC, Kwong PD, Baty D, Chames P, Braibant M, and Barin F
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal immunology, CD4 Antigens, CD4 Lymphocyte Count, Chlorofluorocarbons, Methane, Epitopes immunology, Gene Expression Regulation, Viral physiology, HIV Envelope Protein gp120 immunology, HIV Infections virology, HIV-1 classification, HIV-1 genetics, Humans, Molecular Sequence Data, Phylogeny, Recombinant Proteins, env Gene Products, Human Immunodeficiency Virus immunology, Antibodies, Neutralizing immunology, Conserved Sequence, Epitopes genetics, HIV Antibodies immunology, HIV Infections immunology, HIV-1 immunology
- Abstract
Background: Highly potent broadly neutralizing monoclonal antibodies (bNAbs) have been obtained from individuals infected by HIV-1 group M variants. We analyzed the cross-group neutralization potency of these bNAbs toward non-M primary isolates (PI)., Material and Methods: The sensitivity to neutralization was analyzed in a neutralization assay using TZM-bl cells. Twenty-three bNAbs were used, including reagents targeting the CD4-binding site, the N160 glycan-V1/V2 site, the N332 glycan-V3 site, the membrane proximal external region of gp41, and complex epitopes spanning both env subunits. Two bispecific antibodies that combine the inhibitory activity of an anti-CD4 with that of PG9 or PG16 bNAbs were included in the study (PG9-iMab and PG16-iMab)., Results: Cross-group neutralization was observed only with the bNAbs targeting the N160 glycan-V1/V2 site. Four group O PIs, 1 group N PI, and the group P PI were neutralized by PG9 and/or PG16 or PGT145 at low concentrations (0.04-9.39 μg/mL). None of the non-M PIs was neutralized by the bNAbs targeting other regions at the highest concentration tested, except 10E8 that neutralized weakly 2 group N PIs and 35O22 that neutralized 1 group O PI. The bispecific bNAbs neutralized very efficiently all the non-M PIs with IC50 below 1 μg/mL, except 2 group O strains., Conclusion: The N160 glycan-V1/V2 site is the most conserved neutralizing site within the 4 groups of HIV-1. This makes it an interesting target for the development of HIV vaccine immunogens. The corresponding bNAbs may be useful for immunotherapeutic strategies in patients infected by non-M variants.
- Published
- 2016
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47. The role of neutralizing antibodies in prevention of HIV-1 infection: what can we learn from the mother-to-child transmission context?
- Author
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Braibant M and Barin F
- Subjects
- Animals, Antibodies, Monoclonal immunology, Antibodies, Monoclonal therapeutic use, Antibodies, Neutralizing immunology, Biomedical Research trends, Disease Models, Animal, HIV Antibodies immunology, HIV Infections immunology, Humans, Immunization, Passive, Macaca, Antibodies, Neutralizing therapeutic use, Disease Transmission, Infectious prevention & control, HIV Antibodies therapeutic use, HIV Infections prevention & control, HIV-1 immunology
- Abstract
In most viral infections, protection through existing vaccines is linked to the presence of vaccine-induced neutralizing antibodies (NAbs). However, more than 30 years after the identification of AIDS, the design of an immunogen able to induce antibodies that would neutralize the highly diverse HIV-1 variants remains one of the most puzzling challenges of the human microbiology. The role of antibodies in protection against HIV-1 can be studied in a natural situation that is the mother-to-child transmission (MTCT) context. Indeed, at least at the end of pregnancy, maternal antibodies of the IgG class are passively transferred to the fetus protecting the neonate from new infections during the first weeks or months of life. During the last few years, strong data, presented in this review, have suggested that some NAbs might confer protection toward neonatal HIV-1 infection. In cases of transmission, it has been shown that the viral population that is transmitted from the mother to the infant is usually homogeneous, genetically restricted and resistant to the maternal HIV-1-specific antibodies. Although the breath of neutralization was not associated with protection, it has not been excluded that NAbs toward specific HIV-1 strains might be associated with a lower rate of MTCT. A better identification of the antibody specificities that could mediate protection toward MTCT of HIV-1 would provide important insights into the antibody responses that would be useful for vaccine development. The most convincing data suggesting that NAbs might confer protection against HIV-1 infection have been obtained by experiments of passive immunization of newborn macaques with the first generation of human monoclonal broadly neutralizing antibodies (HuMoNAbs). However, these studies, which included only a few selected subtype B challenge viruses, provide data limited to protection against a very restricted number of isolates and therefore have limitations in addressing the hypervariability of HIV-1. The recent identification of highly potent second-generation cross-clade HuMoNAbs provides a new opportunity to evaluate the efficacy of passive immunization to prevent MTCT of HIV-1.
- Published
- 2013
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48. Cross-group neutralization of HIV-1 and evidence for conservation of the PG9/PG16 epitopes within divergent groups.
- Author
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Braibant M, Gong EY, Plantier JC, Moreau T, Alessandri E, Simon F, and Barin F
- Subjects
- HIV-1 classification, HIV-1 isolation & purification, Humans, Models, Theoretical, Neutralization Tests methods, Antibodies, Neutralizing immunology, Epitopes immunology, HIV Antibodies immunology, HIV Infections immunology, HIV-1 immunology
- Abstract
Objective: HIV-1 has been classified into four groups: M, N, O and P. The aim of this study was to revisit the cross-group neutralization using a highly diverse panel of primary isolates., Design: The panel of viruses included nine HIV-1 group O primary isolates, one recombinant M/O primary isolate, one group N primary isolates, one group P primary isolate, two group M (subtype B) primary isolates and the HIV-1 group M adapted strain MN., Methods: All the viruses were tested for neutralization in TZM-bl cells, using sera issued from patients infected by viruses of group M (n = 11), O (n = 12) and P (n = 1), and a panel of nine human monoclonal broadly neutralizing antibodies (HuMo bNAbs)., Results: Although the primary isolates displayed a wide spectrum of sensitivity to neutralization by the human sera, cross-group neutralization was clearly observed. In contrast, the bNAbs did not show any cross-group neutralization, except PG9 and PG16. Interestingly, the group N prototype strain YBF30 was highly sensitive to neutralization by PG9 (IC50: 0.28 μg/ml) and PG16 (IC50: < 0.12 μg/ml). The interaction between PG9 and key residues of YBF30 was confirmed by molecular modeling., Conclusion: The conservation of the PG9 and PG16 epitopes within groups M and N provides an argument for their relevance as components of a potentially efficient HIV vaccine immunogen.
- Published
- 2013
- Full Text
- View/download PDF
49. Evidence for a continuous drift of the HIV-1 species towards higher resistance to neutralizing antibodies over the course of the epidemic.
- Author
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Bouvin-Pley M, Morgand M, Moreau A, Jestin P, Simonnet C, Tran L, Goujard C, Meyer L, Barin F, and Braibant M
- Subjects
- Antibodies, Monoclonal metabolism, Antibody Specificity, Antigens, Viral biosynthesis, Antigens, Viral genetics, Antigens, Viral metabolism, Cohort Studies, Epidemiological Monitoring, Epitopes genetics, France epidemiology, HIV Infections epidemiology, HIV Infections transmission, HIV-1 genetics, HIV-1 metabolism, Humans, Immunity, Humoral, Immunogenetic Phenomena, Membrane Glycoproteins antagonists & inhibitors, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Phylogeny, RNA, Viral blood, RNA, Viral metabolism, Viral Envelope Proteins antagonists & inhibitors, Viral Envelope Proteins genetics, Viral Envelope Proteins metabolism, Antibodies, Neutralizing metabolism, Epidemics, Genetic Drift, HIV Infections immunology, HIV Infections virology, HIV-1 immunology
- Abstract
We compared the neutralization sensitivity of early/transmitted HIV-1 variants from patients infected by subtype B viruses at 3 periods of the epidemic (1987-1991, 1996-2000, 2006-2010). Infectious pseudotyped viruses expressing envelope glycoproteins representative of the viral quasi-species infecting each patient were tested for sensitivity to neutralization by pools of sera from HIV-1 chronically infected patients and by an updated panel of 13 human monoclonal neutralizing antibodies (HuMoNAbs). A progressive significantly enhanced resistance to neutralization was observed over calendar time, by both human sera and most of the HuMoNAbs tested (b12, VRC01, VRC03, NIH45-46(G54W), PG9, PG16, PGT121, PGT128, PGT145). Despite this evolution, a combination of two HuMoNAbs (NIH45-46(G54W) and PGT128) still would efficiently neutralize the most contemporary transmitted variants. In addition, we observed a significant reduction of the heterologous neutralizing activity of sera from individuals infected most recently (2003-2007) compared to patients infected earlier (1987-1991), suggesting that the increasing resistance of the HIV species to neutralization over time coincided with a decreased immunogenicity. These data provide evidence for an ongoing adaptation of the HIV-1 species to the humoral immunity of the human population, which may add an additional obstacle to the design of an efficient HIV-1 vaccine.
- Published
- 2013
- Full Text
- View/download PDF
50. Naturally occurring substitutions of conserved residues in human immunodeficiency virus type 1 variants of different clades are involved in PG9 and PG16 resistance to neutralization.
- Author
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Thenin S, Roch E, Samleerat T, Moreau T, Chaillon A, Moreau A, Barin F, and Braibant M
- Subjects
- Amino Acid Substitution, Antibodies, Monoclonal immunology, DNA Mutational Analysis, HIV-1 genetics, HIV-1 isolation & purification, Humans, Molecular Sequence Data, Mutagenesis, Site-Directed, Mutant Proteins genetics, Mutant Proteins immunology, Neutralization Tests, RNA, Viral genetics, Sequence Analysis, DNA, Antibodies, Neutralizing immunology, HIV Antibodies immunology, HIV Infections virology, HIV-1 immunology, Mutation, Missense, env Gene Products, Human Immunodeficiency Virus genetics, env Gene Products, Human Immunodeficiency Virus immunology
- Abstract
The recently described anti-human immunodeficiency virus type 1 (HIV-1) human mAb PG9 and PG16 are cross-clade broadly neutralizing. Therefore, it can be postulated that the targeted epitope(s) are highly conserved among variants of the entire group M. We analysed the sensitivity to PG9 and PG16 of pseudotyped viruses carrying envelope glycoproteins from the viral quasispecies of three HIV-1 clade CRF01_AE-infected patients. The broad heterogeneity in sensitivity to PG9 and PG16, despite closely genetically related envelope glycoproteins issued from single individuals, allowed us to identify two gp120 cross-clade conserved residues, a lysine at position 168 in the V2 loop and an isoleucine at position 215 in the C2 region, whose substitutions were associated with resistance to PG9 and PG16. By site-directed mutagenesis, we confirmed both in clades B and CRF01_AE that the substitutions K168E and I215M have a major impact on PG9 and PG16 neutralization sensitivity of pseudotyped viruses.
- Published
- 2012
- Full Text
- View/download PDF
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