Research Overview

Research in our laboratory centers on innate immunity of immunocompromised patients to microbial infection. Our interest in this area traces to my doctoral training during which I isolated and studied human neutrophil-derived antimicrobial proteins and peptides including cathelicidins and the bactericidal/permeability-increasing protein (BPI) that possesses antibacterial and endotoxin-neutralizing activity against Gram-negative bacteria. Spurred by an interest in the functional immaturity of neutrophil function at birth, we have discovered that neutrophils of human newborns are deficient in BPI, that possesses cytotoxic and endotoxin-neutralizing activity towards Gram-negative bacteria. Supplementing human newborn cord blood with recombinant BPI in vitro enhances bactericidal activity against Gram-negative bacteria and markedly reduces bacteria-induced cytokine release, raising the possibility that BPI might represent a potential therapy for newborns with invasive Gram-negative bacterial infection and/or endotoxemia.

Translational work in our lab has recently demonstrated the importance of endotoxin-directed innate immunity in triggering graft-versus-host-disease in neutropenic pediatric and adult patients undergoing myeloablative chemotherapy for hematopoietic stem cell transplantation (bone marrow transplantation). Together with collaborators at the Dana Farber Cancer Institute, we are currently conducting a clinical trial of recombinant BPI (rBPI21, XOMA (U.S.) LLC) as a novel endotoxin antagonist, assessing safety, pharmacokinetics, and impact on endotoxin-directed innate immunity.

Another major innate immune focus of our laboratory is the expression and function of the Toll-like receptor (TLR) system in human newborns. Greater than 2,000,000 infants under the age of 6 months die every year of infection and therefore characterizing mechanisms of susceptibility and approaches to modulating neonatal host defense to prevent and or treat infection are global health priorities. We have discovered a marked impairment in TLR-mediated production of the Th1-polarizing cytokine TNF by human newborn blood monocytes. Remarkably, newborn plasma inhibits TLR2-mediated TNF production from monocytes, reflecting the presence of adenosine, an endogenous purine metabolite. Adenosine induces the secondary messenger cyclic adenosine monophosphate (cAMP), that suppresses TLR-induced TNF production but preserves synthesis of the anti-inflammatory and Th2-polarizing cytokine IL-6. Skewed TLR-induced cytokine responses may significantly contribute to immature neonatal immunity.

In marked contrast to impaired neonatal responses to most TLR agonists, we have discovered that TLR8 agonists, including single stranded viral RNAs and synthetic nucleoside imidazoquinoline compounds, fully activate robust production of TNF and IL-12 by human neonatal antigen-presenting cells, corresponding to robust activation of NF-kB and p38 MAP kinase pathways. Preservation of responses to TLR8 agonists may present unique opportunities for augmenting immunity in the human newborn, particularly as novel vaccine adjuvants that may be active at birth- a major public health priority. We have recently expanded this work to include a tissue engineering approach for in vitro modeling of neonatal antigen-presenting cell and lymphocyte responses to novel vaccine formulations incorporating TLR agonists and nanoparticles.

The overall goal of our work is to identify innate immune pathway defects as potential targets of immunomodulatory therapies to prevent and treat infection in newborns and those exposed to chemoradio-therapy.

About Ofer Levy

Ofer Levy received his MD and PhD degrees from New York University. He completed internship, residency, and clinical fellowship training at Children's Hospital, Boston and a research fellowship at Brigham and Women's Hospital.

Researcher Services

Researcher Areas

  • Innate Immunity of the Human Newborn

Research Departments

Research Divisions

CERTIFICATIONS

  • American Board of Pediatrics, General Pediatrics

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Speer EM, Diago-Navarro E, Ozog LS, Dowling DJ, Hou W, Raheel M, Fries BC, Levy O. Pentoxifylline Alone or in Combination with Gentamicin or Vancomycin Inhibits Live Microbe-Induced Proinflammatory Cytokine Production in Human Cord Blood and Cord Blood Monocytes In Vitro. Antimicrob Agents Chemother. 2018 Dec; 62(12). View abstract
  2. Queenan AM, Dowling DJ, Cheng WK, Faé K, Fernandez J, Flynn PJ, Joshi S, Brightman SE, Ramirez J, Serroyen J, Wiertsema S, Fortanier A, van den Dobbelsteen G, Levy O, Poolman J. Increasing FIM2/3 antigen-content improves efficacy of Bordetella pertussis vaccines in mice in vivo without altering vaccine-induced human reactogenicity biomarkers in vitro. Vaccine. 2018 Nov 23. View abstract
  3. Munoz FM, Van Damme P, Dinleyici E, Clarke E, Kampmann B, Heath PT, Levy O, Leuridan E, Cutland C, Sobanjo-Ter Meulen A, Marchant A. The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs. mSphere. 2018 Nov 07; 3(6). View abstract
  4. Borriello F, van Haren SD, Levy O. First International Precision Vaccines Conference: Multidisciplinary Approaches to Next-Generation Vaccines. mSphere. 2018 08 01; 3(4). View abstract
  5. Schüller SS, Kramer BW, Villamor E, Spittler A, Berger A, Levy O. Immunomodulation to Prevent or Treat Neonatal Sepsis: Past, Present, and Future. Front Pediatr. 2018; 6:199. View abstract
  6. Permar S, Levy O, Kollman TR, Singh A, De Paris K. Early Life HIV-1 Immunization: Providing a Window for Protection Before Sexual Debut. AIDS Res Hum Retroviruses. 2018 Oct; 34(10):823-827. View abstract
  7. Scheid A, Li N, Jeffers C, Borriello F, Joshi S, Ozonoff A, Pettengill M, Levy O. Antimicrobial peptide LL-37 and recombinant human mannose-binding lectin express distinct age- and pathogen-specific antimicrobial activity in human newborn cord blood in vitro. F1000Res. 2018; 7:616. View abstract
  8. Speer EM, Dowling DJ, Xu J, Ozog LS, Mathew JA, Chander A, Yin D, Levy O. Pentoxifylline, dexamethasone and azithromycin demonstrate distinct age-dependent and synergistic inhibition of TLR- and inflammasome-mediated cytokine production in human newborn and adult blood in vitro. PLoS One. 2018; 13(5):e0196352. View abstract
  9. Bennike TB, Bellin MD, Xuan Y, Stensballe A, Møller FT, Beilman GJ, Levy O, Cruz-Monserrate Z, Andersen V, Steen J, Conwell DL, Steen H. A Cost-Effective High-Throughput Plasma and Serum Proteomics Workflow Enables Mapping of the Molecular Impact of Total Pancreatectomy with Islet Autotransplantation. J Proteome Res. 2018 May 04; 17(5):1983-1992. View abstract
  10. Whittaker E, Goldblatt D, McIntyre P, Levy O. Neonatal Immunization: Rationale, Current State, and Future Prospects. Front Immunol. 2018; 9:532. View abstract
  11. Lapidot R, Alawdah L, Köhler JR, Paulson V, Levy O. Hepatic Legionella pneumophila Infection in an Infant With Severe Combined Immunodeficiency. Pediatr Infect Dis J. 2018 Apr; 37(4):356-358. View abstract
  12. Scheid A, Borriello F, Pietrasanta C, Christou H, Diray-Arce J, Pettengill MA, Joshi S, Li N, Bergelson I, Kollmann T, Dowling DJ, Levy O. Adjuvant Effect of Bacille Calmette-Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn. Front Immunol. 2018; 9:29. View abstract
  13. Borriello F, Pietrasanta C, Lai JCY, Walsh LM, Sharma P, O'Driscoll DN, Ramirez J, Brightman S, Pugni L, Mosca F, Burkhart DJ, Dowling DJ, Levy O. Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization. Front Immunol. 2017; 8:1772. View abstract
  14. Nold-Petry CA, Nold MF, Levy O, Kliger Y, Oren A, Borukhov I, Becker C, Wirtz S, Sandhu MK, Neurath M, Dinarello CA. Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation. Front Immunol. 2017; 8:1531. View abstract
  15. Gu XX, Plotkin SA, Edwards KM, Sette A, Mills KHG, Levy O, Sant AJ, Mo A, Alexander W, Lu KT, Taylor CE. Waning Immunity and Microbial Vaccines-Workshop of the National Institute of Allergy and Infectious Diseases. Clin Vaccine Immunol. 2017 Jul; 24(7). View abstract
  16. Pettengill M, Matute JD, Tresenriter M, Hibbert J, Burgner D, Richmond P, Millán JL, Ozonoff A, Strunk T, Currie A, Levy O. Human alkaline phosphatase dephosphorylates microbial products and is elevated in preterm neonates with a history of late-onset sepsis. PLoS One. 2017; 12(4):e0175936. View abstract
  17. Dowling DJ, van Haren SD, Scheid A, Bergelson I, Kim D, Mancuso CJ, Foppen W, Ozonoff A, Fresh L, Theriot TB, Lackner AA, Fichorova RN, Smirnov D, Vasilakos JP, Beaurline JM, Tomai MA, Midkiff CC, Alvarez X, Blanchard JL, Gilbert MH, Aye PP, Levy O. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight. 2017 Mar 23; 2(6):e91020. View abstract
  18. Dowling DJ, Scott EA, Scheid A, Bergelson I, Joshi S, Pietrasanta C, Brightman S, Sanchez-Schmitz G, Van Haren SD, Ninkovic J, Kats D, Guiducci C, de Titta A, Bonner DK, Hirosue S, Swartz MA, Hubbell JA, Levy O. Toll-like receptor 8 agonist nanoparticles mimic immunomodulating effects of the live BCG vaccine and enhance neonatal innate and adaptive immune responses. J Allergy Clin Immunol. 2017 Nov; 140(5):1339-1350. View abstract
  19. Kollmann TR, Kampmann B, Mazmanian SK, Marchant A, Levy O. Protecting the Newborn and Young Infant from Infectious Diseases: Lessons from Immune Ontogeny. Immunity. 2017 03 21; 46(3):350-363. View abstract
  20. Speer EM, Dowling DJ, Ozog LS, Xu J, Yang J, Kennady G, Levy O. Pentoxifylline inhibits TLR- and inflammasome-mediated in vitro inflammatory cytokine production in human blood with greater efficacy and potency in newborns. Pediatr Res. 2017 May; 81(5):806-816. View abstract
  21. Dowling DJ, Sanders H, Cheng WK, Joshi S, Brightman S, Bergelson I, Pietrasanta C, van Haren SD, van Amsterdam S, Fernandez J, van den Dobbelsteen GP, Levy O. A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity. Front Immunol. 2016; 7:562. View abstract
  22. Jans J, Pettengill M, Kim D, van der Made C, de Groot R, Henriet S, de Jonge MI, Ferwerda G, Levy O. Human newborn B cells mount an interferon-a/ß receptor-dependent humoral response to respiratory syncytial virus. J Allergy Clin Immunol. 2017 Jun; 139(6):1997-2000.e4. View abstract
  23. van Haren SD, Dowling DJ, Foppen W, Christensen D, Andersen P, Reed SG, Hershberg RM, Baden LR, Levy O. Age-Specific Adjuvant Synergy: Dual TLR7/8 and Mincle Activation of Human Newborn Dendritic Cells Enables Th1 Polarization. J Immunol. 2016 12 01; 197(11):4413-4424. View abstract
  24. Battersby AJ, Khara J, Wright VJ, Levy O, Kampmann B. Antimicrobial Proteins and Peptides in Early Life: Ontogeny and Translational Opportunities. Front Immunol. 2016; 7:309. View abstract
  25. Saadatian-Elahi M, Aaby P, Shann F, Netea MG, Levy O, Louis J, Picot V, Greenberg M, Warren W. Heterologous vaccine effects. Vaccine. 2016 07 25; 34(34):3923-30. View abstract
  26. Pettengill MA, van Haren SD, Li N, Dowling DJ, Bergelson I, Jans J, Ferwerda G, Levy O. Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells. Innate Immun. 2016 08; 22(6):433-43. View abstract
  27. Goodridge HS, Ahmed SS, Curtis N, Kollmann TR, Levy O, Netea MG, Pollard AJ, van Crevel R, Wilson CB. Harnessing the beneficial heterologous effects of vaccination. Nat Rev Immunol. 2016 06; 16(6):392-400. View abstract
  28. Ganapathi L, Arnold A, Jones S, Patterson A, Graham D, Harper M, Levy O. Use of cidofovir in pediatric patients with adenovirus infection. F1000Res. 2016; 5:758. View abstract
  29. van Haren SD, Ganapathi L, Bergelson I, Dowling DJ, Banks M, Samuels RC, Reed SG, Marshall JD, Levy O. In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant. Cytokine. 2016 07; 83:99-109. View abstract
  30. Pettengill MA, Levy O. Circulating Human Neonatal Naïve B Cells are Deficient in CD73 Impairing Purine Salvage. Front Immunol. 2016; 7:121. View abstract
  31. Fish EN, Flanagan KL, Furman D, Klein SL, Kollmann TR, Jeppesen DL, Levy O, Marchant A, Namachivayam S, Netea MG, Plebanski M, Rowland-Jones SL, Selin LK, Shann F, Whittle HC. Changing oral vaccine to inactivated polio vaccine might increase mortality. Lancet. 2016 Mar 12; 387(10023):1054-1055. View abstract
  32. Oh DY, Dowling DJ, Ahmed S, Choi H, Brightman S, Bergelson I, Berger ST, Sauld JF, Pettengill M, Kho AT, Pollack HJ, Steen H, Levy O. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures. Mol Cell Proteomics. 2016 06; 15(6):1877-94. View abstract
  33. Guinan E, Avigan DE, Soiffer RJ, Bunin NJ, Brennan LL, Bergelson I, Brightman S, Ozonoff A, Scannon PJ, Levy O. Pilot experience with opebacan/rBPI 21 in myeloablative hematopoietic cell transplantation. F1000Res. 2015; 4:1480. View abstract
  34. Dowling DJ, Levy O. Pediatric Vaccine Adjuvants: Components of the Modern Vaccinologist's Toolbox. Pediatr Infect Dis J. 2015 Dec; 34(12):1395-8. View abstract
  35. Nguyen DN, Fuglsang E, Jiang P, Birck MM, Pan X, Kamal SB, Pors SE, Gammelgaard PL, Nielsen DS, Thymann T, Levy O, Frøkiær H, Sangild PT. Oral antibiotics increase blood neutrophil maturation and reduce bacteremia and necrotizing enterocolitis in the immediate postnatal period of preterm pigs. Innate Immun. 2016 Jan; 22(1):51-62. View abstract
  36. Ganapathi L, Van Haren S, Dowling DJ, Bergelson I, Shukla NM, Malladi SS, Balakrishna R, Tanji H, Ohto U, Shimizu T, David SA, Levy O. The Imidazoquinoline Toll-Like Receptor-7/8 Agonist Hybrid-2 Potently Induces Cytokine Production by Human Newborn and Adult Leukocytes. PLoS One. 2015; 10(8):e0134640. View abstract
  37. Amenyogbe N, Levy O, Kollmann TR. Systems vaccinology: a promise for the young and the poor. Philos Trans R Soc Lond B Biol Sci. 2015 Jun 19; 370(1671). View abstract
  38. Bi D, Qiao L, Bergelson I, Ek CJ, Duan L, Zhang X, Albertsson AM, Pettengill M, Kronforst K, Ninkovic J, Goldmann D, Janzon A, Hagberg H, Wang X, Mallard C, Levy O. Staphylococcus epidermidis Bacteremia Induces Brain Injury in Neonatal Mice via Toll-like Receptor 2-Dependent and -Independent Pathways. J Infect Dis. 2015 Nov 01; 212(9):1480-90. View abstract
  39. Levy O, Levy O. Ready to benefit from training: heterologous effects of early life immunization. Trans R Soc Trop Med Hyg. 2015 Jan; 109(1):3-4. View abstract
  40. Pettengill MA, van Haren SD, Levy O. Soluble mediators regulating immunity in early life. Front Immunol. 2014; 5:457. View abstract
  41. Palmer CD, Ninkovic J, Prokopowicz ZM, Mancuso CJ, Marin A, Andrianov AK, Dowling DJ, Levy O. The effect of stable macromolecular complexes of ionic polyphosphazene on HIV Gag antigen and on activation of human dendritic cells and presentation to T-cells. Biomaterials. 2014 Oct; 35(31):8876-8886. View abstract
  42. Dowling DJ, Levy O. Ontogeny of early life immunity. Trends Immunol. 2014 Jul; 35(7):299-310. View abstract
  43. Strunk T, Inder T, Wang X, Burgner D, Mallard C, Levy O. Infection-induced inflammation and cerebral injury in preterm infants. Lancet Infect Dis. 2014 Aug; 14(8):751-762. View abstract
  44. Levy O, Wynn JL. A prime time for trained immunity: innate immune memory in newborns and infants. Neonatology. 2014; 105(2):136-41. View abstract
  45. Jans J, Vissers M, Heldens JG, de Jonge MI, Levy O, Ferwerda G. Fc gamma receptors in respiratory syncytial virus infections: implications for innate immunity. Rev Med Virol. 2014 Jan; 24(1):55-70. View abstract
  46. Levy O, Netea MG. Innate immune memory: implications for development of pediatric immunomodulatory agents and adjuvanted vaccines. Pediatr Res. 2014 Jan; 75(1-2):184-8. View abstract
  47. Guinan EC, Palmer CD, Mancuso CJ, Brennan L, Stoler-Barak L, Kalish LA, Suter EE, Gallington LC, Huhtelin DP, Mansilla M, Schumann RR, Murray JC, Weiss J, Levy O. Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin. Innate Immun. 2014 Oct; 20(7):697-711. View abstract
  48. Pettengill M, Robson S, Tresenriter M, Millán JL, Usheva A, Bingham T, Belderbos M, Bergelson I, Burl S, Kampmann B, Gelinas L, Kollmann T, Bont L, Levy O. Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine. J Biol Chem. 2013 Sep 20; 288(38):27315-26. View abstract
  49. Power Coombs MR, Kronforst K, Levy O. Neonatal host defense against Staphylococcal infections. Clin Dev Immunol. 2013; 2013:826303. View abstract
  50. Kollmann TR, Levy O, Hanekom W. Vaccine-induced immunity in early life. Vaccine. 2013 May 17; 31(21):2481-2. View abstract
  51. Dowling DJ, Tan Z, Prokopowicz ZM, Palmer CD, Matthews MA, Dietsch GN, Hershberg RM, Levy O. The ultra-potent and selective TLR8 agonist VTX-294 activates human newborn and adult leukocytes. PLoS One. 2013; 8(3):e58164. View abstract
  52. Cuenca AG, Wynn JL, Moldawer LL, Levy O. Role of innate immunity in neonatal infection. Am J Perinatol. 2013 Feb; 30(2):105-12. View abstract
  53. Belderbos ME, Levy O, Meyaard L, Bont L. Plasma-mediated immune suppression: a neonatal perspective. Pediatr Allergy Immunol. 2013 Mar; 24(2):102-13. View abstract
  54. Kollmann TR, Levy O, Montgomery RR, Goriely S. Innate immune function by Toll-like receptors: distinct responses in newborns and the elderly. Immunity. 2012 Nov 16; 37(5):771-83. View abstract
  55. Levy O, Goriely S, Kollmann TR. Immune response to vaccine adjuvants during the first year of life. Vaccine. 2013 May 17; 31(21):2500-5. View abstract
  56. Kronforst KD, Mancuso CJ, Pettengill M, Ninkovic J, Power Coombs MR, Stevens C, Otto M, Mallard C, Wang X, Goldmann D, Levy O. A neonatal model of intravenous Staphylococcus epidermidis infection in mice <24 h old enables characterization of early innate immune responses. PLoS One. 2012; 7(9):e43897. View abstract
  57. Nathe KE, Mancuso CJ, Parad R, Van Marter LJ, Martin CR, Stoler-Barak L, Philbin VJ, Phillips MF, Palmer CD, Levy O. Innate immune activation in neonatal tracheal aspirates suggests endotoxin-driven inflammation. Pediatr Res. 2012 Aug; 72(2):203-11. View abstract
  58. Philbin VJ, Dowling DJ, Gallington LC, Cortés G, Tan Z, Suter EE, Chi KW, Shuckett A, Stoler-Barak L, Tomai M, Miller RL, Mansfield K, Levy O. Imidazoquinoline Toll-like receptor 8 agonists activate human newborn monocytes and dendritic cells through adenosine-refractory and caspase-1-dependent pathways. J Allergy Clin Immunol. 2012 Jul; 130(1):195-204.e9. View abstract
  59. Strunk T, Prosser A, Levy O, Philbin V, Simmer K, Doherty D, Charles A, Richmond P, Burgner D, Currie A. Responsiveness of human monocytes to the commensal bacterium Staphylococcus epidermidis develops late in gestation. Pediatr Res. 2012 Jul; 72(1):10-8. View abstract
  60. Belderbos ME, Levy O, Stalpers F, Kimpen JL, Meyaard L, Bont L. Neonatal plasma polarizes TLR4-mediated cytokine responses towards low IL-12p70 and high IL-10 production via distinct factors. PLoS One. 2012; 7(3):e33419. View abstract
  61. Guinan EC, Barbon CM, Kalish LA, Parmar K, Kutok J, Mancuso CJ, Stoler-Barak L, Suter EE, Russell JD, Palmer CD, Gallington LC, Voskertchian A, Vergilio JA, Cole G, Zhu K, D'Andrea A, Soiffer R, Weiss JP, Levy O. Bactericidal/permeability-increasing protein (rBPI21) and fluoroquinolone mitigate radiation-induced bone marrow aplasia and death. Sci Transl Med. 2011 Nov 23; 3(110):110ra118. View abstract
  62. Paludan SR, Levy O, Bowie AG. Toll2011 at Lago di Garda: studying danger sensors by the guard towers at the lake. Nat Immunol. 2011 Aug 18; 12(9):805-8. View abstract
  63. Palmer CD, Guinan EC, Levy O. Deficient expression of bactericidal/permeability-increasing protein in immunocompromised hosts: translational potential of replacement therapy. Biochem Soc Trans. 2011 Aug; 39(4):994-9. View abstract
  64. Sanchez-Schmitz G, Levy O. Development of newborn and infant vaccines. Sci Transl Med. 2011 Jul 06; 3(90):90ps27. View abstract
  65. Palmer CD, Mancuso CJ, Weiss JP, Serhan CN, Guinan EC, Levy O. 17(R)-Resolvin D1 differentially regulates TLR4-mediated responses of primary human macrophages to purified LPS and live E. coli. J Leukoc Biol. 2011 Sep; 90(3):459-70. View abstract
  66. Du X, Fleiss B, Li H, D'angelo B, Sun Y, Zhu C, Hagberg H, Levy O, Mallard C, Wang X. Systemic stimulation of TLR2 impairs neonatal mouse brain development. PLoS One. 2011 May 06; 6(5):e19583. View abstract
  67. Burl S, Townend J, Njie-Jobe J, Cox M, Adetifa UJ, Touray E, Philbin VJ, Mancuso C, Kampmann B, Whittle H, Jaye A, Flanagan KL, Levy O. Age-dependent maturation of Toll-like receptor-mediated cytokine responses in Gambian infants. PLoS One. 2011 Apr 13; 6(4):e18185. View abstract
  68. PrabhuDas M, Adkins B, Gans H, King C, Levy O, Ramilo O, Siegrist CA. Challenges in infant immunity: implications for responses to infection and vaccines. Nat Immunol. 2011 Mar; 12(3):189-94. View abstract
  69. Power Coombs MR, Belderbos ME, Gallington LC, Bont L, Levy O. Adenosine modulates Toll-like receptor function: basic mechanisms and translational opportunities. Expert Rev Anti Infect Ther. 2011 Feb; 9(2):261-9. View abstract
  70. Zhang JP, Yang Y, Levy O, Chen C. Human neonatal peripheral blood leukocytes demonstrate pathogen-specific coordinate expression of TLR2, TLR4/MD2, and MyD88 during bacterial infection in vivo. Pediatr Res. 2010 Dec; 68(6):479-83. View abstract
  71. Picard C, von Bernuth H, Ghandil P, Chrabieh M, Levy O, Arkwright PD, McDonald D, Geha RS, Takada H, Krause JC, Creech CB, Ku CL, Ehl S, Maródi L, Al-Muhsen S, Al-Hajjar S, Al-Ghonaium A, Day-Good NK, Holland SM, Gallin JI, Chapel H, Speert DP, Rodriguez-Gallego C, Colino E, Garty BZ, Roifman C, Hara T, Yoshikawa H, Nonoyama S, Domachowske J, Issekutz AC, Tang M, Smart J, Zitnik SE, Hoarau C, Kumararatne DS, Thrasher AJ, Davies EG, Bethune C, Sirvent N, de Ricaud D, Camcioglu Y, Vasconcelos J, Guedes M, Vitor AB, Rodrigo C, Almazán F, Méndez M, Aróstegui JI, Alsina L, Fortuny C, Reichenbach J, Verbsky JW, Bossuyt X, Doffinger R, Abel L, Puel A, Casanova JL. Clinical features and outcome of patients with IRAK-4 and MyD88 deficiency. Medicine (Baltimore). 2010 Nov; 89(6):403-25. View abstract
  72. Strunk T, Richmond P, Prosser A, Simmer K, Levy O, Burgner D, Currie A. Method of bacterial killing differentially affects the human innate immune response to Staphylococcus epidermidis. Innate Immun. 2011 Dec; 17(6):508-16. View abstract
  73. Wynn JL, Levy O. Role of innate host defenses in susceptibility to early-onset neonatal sepsis. Clin Perinatol. 2010 Jun; 37(2):307-37. View abstract
  74. Strunk T, Power Coombs MR, Currie AJ, Richmond P, Golenbock DT, Stoler-Barak L, Gallington LC, Otto M, Burgner D, Levy O. TLR2 mediates recognition of live Staphylococcus epidermidis and clearance of bacteremia. PLoS One. 2010 Apr 09; 5(4):e10111. View abstract
  75. Belderbos M, Levy O, Bont L. Neonatal innate immunity in allergy development. Curr Opin Pediatr. 2009 Dec; 21(6):762-9. View abstract
  76. Stanietsky N, Simic H, Arapovic J, Toporik A, Levy O, Novik A, Levine Z, Beiman M, Dassa L, Achdout H, Stern-Ginossar N, Tsukerman P, Jonjic S, Mandelboim O. The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity. Proc Natl Acad Sci U S A. 2009 Oct 20; 106(42):17858-63. View abstract
  77. Demirjian A, Levy O. Neonatal vaccination: a once in a lifetime opportunity. Pediatr Infect Dis J. 2009 Sep; 28(9):833-5. View abstract
  78. Kliger Y, Levy O, Oren A, Ashkenazy H, Tiran Z, Novik A, Rosenberg A, Amir A, Wool A, Toporik A, Schreiber E, Eshel D, Levine Z, Cohen Y, Nold-Petry C, Dinarello CA, Borukhov I. Peptides modulating conformational changes in secreted chaperones: from in silico design to preclinical proof of concept. Proc Natl Acad Sci U S A. 2009 Aug 18; 106(33):13797-801. View abstract
  79. Nathe KE, Parad R, Van Marter LJ, Lund CA, Suter EE, Hernandez-diaz S, Boush EB, Ikonomu E, Gallington L, Morey JA, Zeman AM, Mcnamara M, Levy O. Endotoxin-directed innate immunity in tracheal aspirates of mechanically ventilated human neonates. Pediatr Res. 2009 Aug; 66(2):191-6. View abstract
  80. Philbin VJ, Levy O. Developmental biology of the innate immune response: implications for neonatal and infant vaccine development. Pediatr Res. 2009 May; 65(5 Pt 2):98R-105R. View abstract
  81. Demirjian A, Levy O. Safety and efficacy of neonatal vaccination. Eur J Immunol. 2009 Jan; 39(1):36-46. View abstract
  82. Canny G, Levy O. Bactericidal/permeability-increasing protein (BPI) and BPI homologs at mucosal sites. Trends Immunol. 2008 Nov; 29(11):541-7. View abstract
  83. Demirjian A, Levy O. Novel vaccines: bridging research, development and production. Expert Rev Vaccines. 2008 Nov; 7(9):1321-4. View abstract
  84. Pai SY, Levy O, Jabara HH, Glickman JN, Stoler-Barak L, Sachs J, Nurko S, Orange JS, Geha RS. Allogeneic transplantation successfully corrects immune defects, but not susceptibility to colitis, in a patient with nuclear factor-kappaB essential modulator deficiency. J Allergy Clin Immunol. 2008 Dec; 122(6):1113-1118.e1. View abstract
  85. Wynn JL, Scumpia PO, Winfield RD, Delano MJ, Kelly-Scumpia K, Barker T, Ungaro R, Levy O, Moldawer LL. Defective innate immunity predisposes murine neonates to poor sepsis outcome but is reversed by TLR agonists. Blood. 2008 Sep 01; 112(5):1750-8. View abstract
  86. Philbin VJ, Levy O. Immunostimulatory activity of Toll-like receptor 8 agonists towards human leucocytes: basic mechanisms and translational opportunities. Biochem Soc Trans. 2007 Dec; 35(Pt 6):1485-91. View abstract
  87. Gonzalez M, Gueguen Y, Destoumieux-Garzón D, Romestand B, Fievet J, Pugnière M, Roquet F, Escoubas JM, Vandenbulcke F, Levy O, Sauné L, Bulet P, Bachère E. Evidence of a bactericidal permeability increasing protein in an invertebrate, the Crassostrea gigas Cg-BPI. Proc Natl Acad Sci U S A. 2007 Nov 06; 104(45):17759-64. View abstract
  88. Levy O, Elsbach P. Bactericidal/permeability-increasing protein in host defense and its efficacy in the treatment of bacterial sepsis. Curr Infect Dis Rep. 2007 Oct; 3(5):407-12. View abstract
  89. Ku CL, von Bernuth H, Picard C, Zhang SY, Chang HH, Yang K, Chrabieh M, Issekutz AC, Cunningham CK, Gallin J, Holland SM, Roifman C, Ehl S, Smart J, Tang M, Barrat FJ, Levy O, McDonald D, Day-Good NK, Miller R, Takada H, Hara T, Al-Hajjar S, Al-Ghonaium A, Speert D, Sanlaville D, Li X, Geissmann F, Vivier E, Maródi L, Garty BZ, Chapel H, Rodriguez-Gallego C, Bossuyt X, Abel L, Puel A, Casanova JL. Selective predisposition to bacterial infections in IRAK-4-deficient children: IRAK-4-dependent TLRs are otherwise redundant in protective immunity. J Exp Med. 2007 Oct 01; 204(10):2407-22. View abstract
  90. Strunk T, Richmond P, Simmer K, Currie A, Levy O, Burgner D. Neonatal immune responses to coagulase-negative staphylococci. Curr Opin Infect Dis. 2007 Aug; 20(4):370-5. View abstract
  91. Levy O. Innate immunity of the newborn: basic mechanisms and clinical correlates. Nat Rev Immunol. 2007 May; 7(5):379-90. View abstract
  92. Srivastava A, Casey H, Johnson N, Levy O, Malley R. Recombinant bactericidal/permeability-increasing protein rBPI21 protects against pneumococcal disease. Infect Immun. 2007 Jan; 75(1):342-9. View abstract
  93. Ezernitchi AV, Vaknin I, Cohen-Daniel L, Levy O, Manaster E, Halabi A, Pikarsky E, Shapira L, Baniyash M. TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs. J Immunol. 2006 Oct 01; 177(7):4763-72. View abstract
  94. Levy O, Coughlin M, Cronstein BN, Roy RM, Desai A, Wessels MR. The adenosine system selectively inhibits TLR-mediated TNF-alpha production in the human newborn. J Immunol. 2006 Aug 01; 177(3):1956-66. View abstract
  95. Angelone DF, Wessels MR, Coughlin M, Suter EE, Valentini P, Kalish LA, Levy O. Innate immunity of the human newborn is polarized toward a high ratio of IL-6/TNF-alpha production in vitro and in vivo. Pediatr Res. 2006 Aug; 60(2):205-9. View abstract
  96. Levy O, Suter EE, Miller RL, Wessels MR. Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells. Blood. 2006 Aug 15; 108(4):1284-90. View abstract
  97. Fox LM, Wingerter S, Ahmed A, Arnold A, Chou J, Rhein L, Levy O. Neonatal babesiosis: case report and review of the literature. Pediatr Infect Dis J. 2006 Feb; 25(2):169-73. View abstract
  98. Canny G, Cario E, Lennartsson A, Gullberg U, Brennan C, Levy O, Colgan SP. Functional and biochemical characterization of epithelial bactericidal/permeability-increasing protein. Am J Physiol Gastrointest Liver Physiol. 2006 Mar; 290(3):G557-67. View abstract
  99. Orange JS, Levy O, Geha RS. Human disease resulting from gene mutations that interfere with appropriate nuclear factor-kappaB activation. Immunol Rev. 2005 Feb; 203:21-37. View abstract
  100. Levy O. Innate immunity of the human newborn: distinct cytokine responses to LPS and other Toll-like receptor agonists. J Endotoxin Res. 2005; 11(2):113-6. View abstract
  101. Levy O, Zarember KA, Roy RM, Cywes C, Godowski PJ, Wessels MR. Selective impairment of TLR-mediated innate immunity in human newborns: neonatal blood plasma reduces monocyte TNF-alpha induction by bacterial lipopeptides, lipopolysaccharide, and imiquimod, but preserves the response to R-848. J Immunol. 2004 Oct 01; 173(7):4627-34. View abstract
  102. Orange JS, Levy O, Brodeur SR, Krzewski K, Roy RM, Niemela JE, Fleisher TA, Bonilla FA, Geha RS. Human nuclear factor kappa B essential modulator mutation can result in immunodeficiency without ectodermal dysplasia. J Allergy Clin Immunol. 2004 Sep; 114(3):650-6. View abstract
  103. Levy O. Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes. J Leukoc Biol. 2004 Nov; 76(5):909-25. View abstract
  104. Levy O. Genetic screening for susceptibility to infection in the NICU setting. Pediatr Res. 2004 Apr; 55(4):546-8. View abstract
  105. Levy O, Jean-Jacques RM, Cywes C, Sisson RB, Zarember KA, Godowski PJ, Christianson JL, Guttormsen HK, Carroll MC, Nicholson-Weller A, Wessels MR. Critical role of the complement system in group B streptococcus-induced tumor necrosis factor alpha release. Infect Immun. 2003 Nov; 71(11):6344-53. View abstract
  106. Levy O, Teixeira-Pinto A, White ML, Carroll SF, Lehmann L, Wypij D, Guinan E. Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation. Pediatr Infect Dis J. 2003 Nov; 22(11):978-81. View abstract
  107. Levy O, Orange JS, Hibberd P, Steinberg S, LaRussa P, Weinberg A, Wilson SB, Shaulov A, Fleisher G, Geha RS, Bonilla FA, Exley M. Disseminated varicella infection due to the vaccine strain of varicella-zoster virus, in a patient with a novel deficiency in natural killer T cells. J Infect Dis. 2003 Oct 01; 188(7):948-53. View abstract
  108. Levy O, Canny G, Serhan CN, Colgan SP. Expression of BPI (bactericidal/permeability-increasing protein) in human mucosal epithelia. Biochem Soc Trans. 2003 Aug; 31(Pt 4):795-800. View abstract
  109. Gonen-Gross T, Achdout H, Gazit R, Hanna J, Mizrahi S, Markel G, Goldman-Wohl D, Yagel S, Horejsí V, Levy O, Baniyash M, Mandelboim O. Complexes of HLA-G protein on the cell surface are important for leukocyte Ig-like receptor-1 function. J Immunol. 2003 Aug 01; 171(3):1343-51. View abstract
  110. Ofer Levy, Armando Teixeira-Pinto, Mark L. White, Stephen F. Carroll, Leslie Lehmann, David Wypij, and Eva Guinan. Endotoxemia and elevation of lipopolysachharide-binding protein after hematopoietic stem cell transplantation. Pediatric Infectious Disease Journal. 2003; 22:978-981. View abstract
  111. Jerrold Weiss, Peter Elsbach, and Ofer Levy. Journeys in the study of antibacterial host defenses: Conserved mechanisms, evolving insights and potential therapeutic opportunities [review]. Recent Research Developments in Antimicrobial Agents & Chemotherapy. 2003; 6:1-38. View abstract
  112. Ofer Levy, Geraldine Canny, Charles Serhan, and Sean Colgan. Expression of BPI by human mucosal epithelia [review]. Biochemical Society Transactions. 2003; 31:795-800. View abstract
  113. Ofer Levy, Kol Zarember, Rochelle Jean-Jacques, Dimitri Sigounas, Colette Cywes, Paul Godowski, and Michael R. Wessels. Newborn cord blood demonstrates impaired TNF responses to multiple pathogen-assocaited molecular pattern molecules (PAMPs) despite normal expression of monocyte Toll-like receptos 1 and 2, MD-2, MyD88 and TIRAP. Pediatric Research: Abstracts of the Pediatric Academic Societies' Annual Meeting. 2003; 350A. View abstract
  114. Ofer Levy, Jordan S. Orange, Patricia Hibberd, Sharon Steinberg, Phillip LaRussa, Adriana Weinberg, S. Brian Wilson, Angela Shaulov, Gary Fleisher, Raif S. Geha, Francisco Bonilla, Mark Exley. Disseminated varicella infection due to vaccine (Oka) strain varicella zoster virus in a patient with a novel deficiency in natural killer T cells. Journal of Infectious Diseases. 2003; 188:948-953. View abstract
  115. Levy O. Impaired innate immunity at birth: deficiency of bactericidal/permeability-increasing protein (BPI) in the neutrophils of newborns. Pediatr Res. 2002 Jun; 51(6):667-9. View abstract
  116. Levy O, Sisson RB, Fryer HE, Goldmann D, Valore E, Ganz T, White ML, Carroll SF, Lehmann L, Guinan EC. Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils. Transplantation. 2002 May 15; 73(9):1522-6. View abstract
  117. Canny G, Levy O, Furuta GT, Narravula-Alipati S, Sisson RB, Serhan CN, Colgan SP. Lipid mediator-induced expression of bactericidal/ permeability-increasing protein (BPI) in human mucosal epithelia. Proc Natl Acad Sci U S A. 2002 Mar 19; 99(6):3902-7. View abstract
  118. Levy O, Bourquin JP, McQueen A, Cantor AB, Lachenauer C, Malley R. Fatal disseminated Candida lusitaniae infection in an infant with chronic granulomatous disease. Pediatr Infect Dis J. 2002 Mar; 21(3):262-4. View abstract
  119. Levy O. Therapeutic potential of the bactericidal/permeability-increasing protein. Expert Opin Investig Drugs. 2002 Feb; 11(2):159-67. View abstract
  120. Ofer Levy, Jean-Pierre Bourquin, Alisa McQueen, Allan B. Cantor, Catherine Lauchenauer, and Richard Malley. Fatal disseminated Candida lusitania infection in an infant with chronic granulomatous disease. Pediatric Infectious Disease Journal. 2002; 21:262-264. View abstract
  121. Geraldine Canny, Ofer Levy, Glenn T. Furuta, Sailaja Narravula-Alipati, Richard B. Sisson, Charles N. Serhan, and Sean P. Colgan. Lipid-mediator-induced expression of bactericidal/permeability-increasing protein (BPI) in human mucosal epithelia. Proceedings of the National Academy of Sciences. 2002; 99:3902-3907. View abstract
  122. Ofer Levy and Peter Elsbach. BPI in host defense and its efficacy in the treatment of bacterial sepsis [review]. Current Infectious Disease Reports. 2001; 3:407-412. View abstract
  123. Levy O. A neutrophil-derived anti-infective molecule: bactericidal/permeability-increasing protein. Antimicrob Agents Chemother. 2000 Nov; 44(11):2925-31. View abstract
  124. Levy O. Antimicrobial proteins and peptides of blood: templates for novel antimicrobial agents. Blood. 2000 Oct 15; 96(8):2664-72. View abstract
  125. Levy O, Sisson RB, Kenyon J, Eichenwald E, Macone AB, Goldmann D. Enhancement of neonatal innate defense: effects of adding an N-terminal recombinant fragment of bactericidal/permeability-increasing protein on growth and tumor necrosis factor-inducing activity of gram-negative bacteria tested in neonatal cord blood ex vivo. Infect Immun. 2000 Sep; 68(9):5120-5. View abstract
  126. Ofer Levy. A neutrophil-derived anti-infective molecule: bactericidal/permeability-increasing protein [review]. Antimicrobial Agenst and Chemotherapy. 2000; 44:2925-2931. View abstract
  127. Levy O, Martin S, Eichenwald E, Ganz T, Valore E, Carroll SF, Lee K, Goldmann D, Thorne GM. Impaired innate immunity in the newborn: newborn neutrophils are deficient in bactericidal/permeability-increasing protein. Pediatrics. 1999 Dec; 104(6):1327-33. View abstract
  128. Jerrold Weiss, Peter Elsbach, and Ofer Levy. Oxygen-independent antimicrobial systems of phagocytes. Inflammation: Basic Principles and Clinical Correlates. 1999; 801-817. View abstract
  129. Ofer Levy. Therapeutic uses of BPI protein products in BPI-deficient humans. 1999. View abstract
  130. Levy O. Antibiotic proteins of polymorphonuclear leukocytes. Eur J Haematol. 1996 May; 56(5):263-77. View abstract
  131. Ofer Levy. Antibacterial 15 kDa protein isoforms (p15s) of rabbit polymorphonuclear leukocytes. 1996. View abstract
  132. Yvette Weinrauch, Jerrold Weiss, Amy Forman, Kol Zarember, Ofer Levy, and Peter Elsbach. Extracellular accumulation of potently microbicidal bactericidal/permeability-increasing protein (BPI) and p15s in an evolving sterile rabbit peritoneal inflammatory exudate. Journal of Clinical Investigation. 1995; 95:1916-1924. View abstract
  133. Ofer Levy, Chean Eng Ooi, Peter Elsbach, Martin E. Doerfler, Robert I. Lehrer, and Jerrold Weiss. Antibacterial proteins of granulaocytes differ in interaction with endotoxin: comparison of BPI, p15s, and defensins. Journal of Immunology. 1995; 154:5403-5410. View abstract
  134. Levy O, Ooi CE, Weiss J, Lehrer RI, Elsbach P. Individual and synergistic effects of rabbit granulocyte proteins on Escherichia coli. J Clin Invest. 1994 Aug; 94(2):672-82. View abstract
  135. Peter Elsbach, Jerrold Weiss, and Ofer Levy. Integration of antimicrobial host defenses against Gram-negative bacteria [review]. Trends in Microbiology. 1994; 2:324-328. View abstract
  136. Levy O, Weiss J, Ooi CE, Elsbach P. Structural characterization of BPI-modulating 15 kDa proteins from rabbit polymorphonuclear leukocytes: identification of a novel family of leukocyte proteins. Agents Actions. 1993; 39 Spec No:C207-10. View abstract
  137. Ofer Levy, Jerrold Weiss, Kol Zarember, Chean Eng Ooi, and Peter Elsbach. Antibacterial 15 kDa protein isoforms (p15s) are members of a novel family of leukocyte proteins. Journal of Biological Chemistry. 1993; 268:6058-6063. View abstract
  138. Chean Eng Ooi, Jerrold Weiss, Ofer Levy, and Peter Elsbach. Isolation of two isoforms of a novel 15 kDa protein from rabbit polymorphonuclear leukocytes that modulates the antibacterial actions of other leukocyte proteins. Journal of Biological Chemistry. 1990; 265:15956-15962. View abstract