Early Interferon-beta Treatment for West-Nile Virus Infection

Summary

West Nile virus (WNV) is a mosquito-borne virus which in majority of cases causes only self-limited disease. Despite that, in minority of cases (\~0.5%) it can infect the brain and cause severe and even life-threatening disease (neuroinvasive disease). Recent study has shown that up to 40% of WNV patients who develop neuroinvasive disease, have antibodies against Interferons (anti-Type I interferon autoantibodies), which neutralizes interferons, and could explain the development of severe disease. The investigators therefore assume that early treatment with interferon beta (the type of interferon against which most patients do not have neutralizing antibodies) could prevent the development of severe neuroinvasive WNV disease.

Timeline

Start

2024-07-14

Primary completion

2025-07-14

Completion

2025-12-31

Publications

• Background Gervais A, Rovida F, Avanzini MA, Croce S, Marchal A, Lin SC, Ferrari A, Thorball CW, Constant O, Le Voyer T, Philippot Q, Rosain J, Angelini M, Perez Lorenzo M, Bizien L, Achille C, Trespidi F, Burdino E, Cassaniti I, Lilleri D, Fornara C, Sammartino JC, Cereda D, Marrocu C, Piralla A, Valsecchi C, Ricagno S, Cogo P, Neth O, Marin-Cruz I, Pacenti M, Sinigaglia A, Trevisan M, Volpe A, Marzollo A, Conti F, Lazzarotto T, Pession A, Viale P, Fellay J, Ghirardello S, Aubart M, Ghisetti V, Aiuti A, Jouanguy E, Bastard P, Percivalle E, Baldanti F, Puel A, MacDonald MR, Rice CM, Rossini G, Murray KO, Simonin Y, Nagy A, Barzon L, Abel L, Diamond MS, Cobat A, Zhang SY, Casanova JL, Borghesi A. Autoantibodies neutralizing type I IFNs underlie West Nile virus encephalitis in approximately 40% of patients. J Exp Med. 2023 Sep 4;220(9):e20230661. doi: 10.1084/jem.20230661. Epub 2023 Jun 22.
• Background Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10.
• Background Samuel MA, Diamond MS. Alpha/beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J Virol. 2005 Nov;79(21):13350-61. doi: 10.1128/JVI.79.21.13350-13361.2005.
• Background Bastard P, Rosen LB, Zhang Q, Michailidis E, Hoffmann HH, Zhang Y, Dorgham K, Philippot Q, Rosain J, Beziat V, Manry J, Shaw E, Haljasmagi L, Peterson P, Lorenzo L, Bizien L, Trouillet-Assant S, Dobbs K, de Jesus AA, Belot A, Kallaste A, Catherinot E, Tandjaoui-Lambiotte Y, Le Pen J, Kerner G, Bigio B, Seeleuthner Y, Yang R, Bolze A, Spaan AN, Delmonte OM, Abers MS, Aiuti A, Casari G, Lampasona V, Piemonti L, Ciceri F, Bilguvar K, Lifton RP, Vasse M, Smadja DM, Migaud M, Hadjadj J, Terrier B, Duffy D, Quintana-Murci L, van de Beek D, Roussel L, Vinh DC, Tangye SG, Haerynck F, Dalmau D, Martinez-Picado J, Brodin P, Nussenzweig MC, Boisson-Dupuis S, Rodriguez-Gallego C, Vogt G, Mogensen TH, Oler AJ, Gu J, Burbelo PD, Cohen JI, Biondi A, Bettini LR, D'Angio M, Bonfanti P, Rossignol P, Mayaux J, Rieux-Laucat F, Husebye ES, Fusco F, Ursini MV, Imberti L, Sottini A, Paghera S, Quiros-Roldan E, Rossi C, Castagnoli R, Montagna D, Licari A, Marseglia GL, Duval X, Ghosn J; HGID Lab; NIAID-USUHS Immune Response to COVID Group; COVID Clinicians; COVID-STORM Clinicians; Imagine COVID Group; French COVID Cohort Study Group; Milieu Interieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19 Biobank; COVID Human Genetic Effort; Tsang JS, Goldbach-Mansky R, Kisand K, Lionakis MS, Puel A, Zhang SY, Holland SM, Gorochov G, Jouanguy E, Rice CM, Cobat A, Notarangelo LD, Abel L, Su HC, Casanova JL. Autoantibodies against type I IFNs in patients with life-threatening COVID-19. Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24.
• Background Bastard P, Gervais A, Le Voyer T, Rosain J, Philippot Q, Manry J, Michailidis E, Hoffmann HH, Eto S, Garcia-Prat M, Bizien L, Parra-Martinez A, Yang R, Haljasmagi L, Migaud M, Sarekannu K, Maslovskaja J, de Prost N, Tandjaoui-Lambiotte Y, Luyt CE, Amador-Borrero B, Gaudet A, Poissy J, Morel P, Richard P, Cognasse F, Troya J, Trouillet-Assant S, Belot A, Saker K, Garcon P, Riviere JG, Lagier JC, Gentile S, Rosen LB, Shaw E, Morio T, Tanaka J, Dalmau D, Tharaux PL, Sene D, Stepanian A, Megarbane B, Triantafyllia V, Fekkar A, Heath JR, Franco JL, Anaya JM, Sole-Violan J, Imberti L, Biondi A, Bonfanti P, Castagnoli R, Delmonte OM, Zhang Y, Snow AL, Holland SM, Biggs C, Moncada-Velez M, Arias AA, Lorenzo L, Boucherit S, Coulibaly B, Anglicheau D, Planas AM, Haerynck F, Duvlis S, Nussbaum RL, Ozcelik T, Keles S, Bousfiha AA, El Bakkouri J, Ramirez-Santana C, Paul S, Pan-Hammarstrom Q, Hammarstrom L, Dupont A, Kurolap A, Metz CN, Aiuti A, Casari G, Lampasona V, Ciceri F, Barreiros LA, Dominguez-Garrido E, Vidigal M, Zatz M, van de Beek D, Sahanic S, Tancevski I, Stepanovskyy Y, Boyarchuk O, Nukui Y, Tsumura M, Vidaur L, Tangye SG, Burrel S, Duffy D, Quintana-Murci L, Klocperk A, Kann NY, Shcherbina A, Lau YL, Leung D, Coulongeat M, Marlet J, Koning R, Reyes LF, Chauvineau-Grenier A, Venet F, Monneret G, Nussenzweig MC, Arrestier R, Boudhabhay I, Baris-Feldman H, Hagin D, Wauters J, Meyts I, Dyer AH, Kennelly SP, Bourke NM, Halwani R, Sharif-Askari NS, Dorgham K, Sallette J, Sedkaoui SM, AlKhater S, Rigo-Bonnin R, Morandeira F, Roussel L, Vinh DC, Ostrowski SR, Condino-Neto A, Prando C, Bonradenko A, Spaan AN, Gilardin L, Fellay J, Lyonnet S, Bilguvar K, Lifton RP, Mane S; HGID Lab; COVID Clinicians; COVID-STORM Clinicians; NIAID Immune Response to COVID Group; NH-COVAIR Study Group; Danish CHGE; Danish Blood Donor Study; St. James's Hospital; SARS CoV2 Interest group; French COVID Cohort Study Group; Imagine COVID-Group; Milieu Interieur Consortium; CoV-Contact Cohort; Amsterdam UMC Covid-19; Biobank Investigators; COVID Human Genetic Effort; CONSTANCES cohort; 3C-Dijon Study; Cerba Health-Care; Etablissement du Sang study group; Anderson MS, Boisson B, Beziat V, Zhang SY, Vandreakos E, Hermine O, Pujol A, Peterson P, Mogensen TH, Rowen L, Mond J, Debette S, de Lamballerie X, Duval X, Mentre F, Zins M, Soler-Palacin P, Colobran R, Gorochov G, Solanich X, Susen S, Martinez-Picado J, Raoult D, Vasse M, Gregersen PK, Piemonti L, Rodriguez-Gallego C, Notarangelo LD, Su HC, Kisand K, Okada S, Puel A, Jouanguy E, Rice CM, Tiberghien P, Zhang Q, Cobat A, Abel L, Casanova JL. Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths. Sci Immunol. 2021 Aug 19;6(62):eabl4340. doi: 10.1126/sciimmunol.abl4340.
• Background Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T, Bizien L, Manry J, Rosain J, Philippot Q, Goavec K, Padey B, Cupic A, Laurent E, Saker K, Vanker M, Sarekannu K; COVID Human Genetic Effort; Etablissement Francais du Sang Study Group; Constances Cohort; 3C-Dijon Study; Cerba HealthCare Group; Lyon Antigrippe Working Group; REIPI INF Working Group; Garcia-Salum T, Ferres M, Le Corre N, Sanchez-Cespedes J, Balsera-Manzanero M, Carratala J, Retamar-Gentil P, Abelenda-Alonso G, Valiente A, Tiberghien P, Zins M, Debette S, Meyts I, Haerynck F, Castagnoli R, Notarangelo LD, Gonzalez-Granado LI, Dominguez-Pinilla N, Andreakos E, Triantafyllia V, Rodriguez-Gallego C, Sole-Violan J, Ruiz-Hernandez JJ, Rodriguez de Castro F, Ferreres J, Briones M, Wauters J, Vanderbeke L, Feys S, Kuo CY, Lei WT, Ku CL, Tal G, Etzioni A, Hanna S, Fournet T, Casalegno JS, Queromes G, Argaud L, Javouhey E, Rosa-Calatrava M, Cordero E, Aydillo T, Medina RA, Kisand K, Puel A, Jouanguy E, Abel L, Cobat A, Trouillet-Assant S, Garcia-Sastre A, Casanova JL. Autoantibodies against type I IFNs in patients with critical influenza pneumonia. J Exp Med. 2022 Nov 7;219(11):e20220514. doi: 10.1084/jem.20220514. Epub 2022 Sep 16.
• Background Bastard P, Michailidis E, Hoffmann HH, Chbihi M, Le Voyer T, Rosain J, Philippot Q, Seeleuthner Y, Gervais A, Materna M, de Oliveira PMN, Maia MLS, Dinis Ano Bom AP, Azamor T, Araujo da Conceicao D, Goudouris E, Homma A, Slesak G, Schafer J, Pulendran B, Miller JD, Huits R, Yang R, Rosen LB, Bizien L, Lorenzo L, Chrabieh M, Erazo LV, Rozenberg F, Jeljeli MM, Beziat V, Holland SM, Cobat A, Notarangelo LD, Su HC, Ahmed R, Puel A, Zhang SY, Abel L, Seligman SJ, Zhang Q, MacDonald MR, Jouanguy E, Rice CM, Casanova JL. Auto-antibodies to type I IFNs can underlie adverse reactions to yellow fever live attenuated vaccine. J Exp Med. 2021 Apr 5;218(4):e20202486. doi: 10.1084/jem.20202486.
• Background de Weerd NA, Vivian JP, Nguyen TK, Mangan NE, Gould JA, Braniff SJ, Zaker-Tabrizi L, Fung KY, Forster SC, Beddoe T, Reid HH, Rossjohn J, Hertzog PJ. Structural basis of a unique interferon-beta signaling axis mediated via the receptor IFNAR1. Nat Immunol. 2013 Sep;14(9):901-7. doi: 10.1038/ni.2667. Epub 2013 Jul 21.
• Results Kalil AC, Devetten MP, Singh S, Lesiak B, Poage DP, Bargenquast K, Fayad P, Freifeld AG. Use of interferon-alpha in patients with West Nile encephalitis: report of 2 cases. Clin Infect Dis. 2005 Mar 1;40(5):764-6. doi: 10.1086/427945. Epub 2005 Feb 7.
• Results Reis G, Moreira Silva EAS, Medeiros Silva DC, Thabane L, Campos VHS, Ferreira TS, Santos CVQ, Nogueira AMR, Almeida APFG, Savassi LCM, Figueiredo-Neto AD, Dias ACF, Freire Junior AM, Bitaraes C, Milagres AC, Callegari ED, Simplicio MIC, Ribeiro LB, Oliveira R, Harari O, Wilson LA, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Limbrick-Oldfield EH, Kanters S, Guyatt GH, Rayner CR, Kandel C, Biondi MJ, Kozak R, Hansen B, Zahoor MA, Arora P, Hislop C, Choong I, Feld JJ, Mills EJ, Glenn JS; TOGETHER Investigators. Early Treatment with Pegylated Interferon Lambda for Covid-19. N Engl J Med. 2023 Feb 9;388(6):518-528. doi: 10.1056/NEJMoa2209760.
• Results Bastard P, Levy R, Henriquez S, Bodemer C, Szwebel TA, Casanova JL. Interferon-beta Therapy in a Patient with Incontinentia Pigmenti and Autoantibodies against Type I IFNs Infected with SARS-CoV-2. J Clin Immunol. 2021 Jul;41(5):931-933. doi: 10.1007/s10875-021-01023-5. Epub 2021 Mar 25. No abstract available.

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