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Research Background

Dr. David Dowling is an immunologist and vaccinologist, Instructor in Pediatrics at Harvard Medical School and a faculty in the Precision Vaccine Program, Division of Infectious Diseases, Boston Children's Hospital. Dr. Dowling obtained a B.Sc. in Biotechnology (Hons) and Ph.D. in Immunology/Vaccinology/Parasitology at Dublin City University (in 2009), where his graduate work made groundbreaking progress in characterizing the immune-polarizing effects of parasite proteins and development of anti-helminth vaccines. David completed his postdoctoral research in the laboratory of Dr. Levy in the Division of Infectious Diseases, Boston Children’s Hospital, where he pioneered innovative use of primary human in vitro modeling, early life animal models in vivo, novel vaccine formulation strategies and multi-omics data integration to develop adjuvanted vaccines targeted to vulnerable populations. His work has resulted in multiple first-authored publications in journals such as the Vaccine, Journal of Clinical Investigation Insight, Journal of Immunology, ImmunoHorizons, Biomaterials, Molecular & Cellular Proteomics, the Journal of Allergy & Clinical Immunology and Trends in Immunology and numerous patent applications of novel intellectual property. David has played a key role in the conception and initiation of BCH’s Adjuvant Discovery (since 2014) and Development Programs (since 2018), NIH-funded contracts, aimed at discovering/developing novel small molecule adjuvants and formulating them to enhance immunization against pertussis and influenza in infants and the elderly, respectively. David is also a formal Fellow of the American Association of Immunologists AAI Public Policy Program, with a special focus on vaccinology, public and political awareness and NIH funding advocacy.

Publications

  1. Protocol for measuring anti-fentanyl antibodies in mouse serum by enzyme-linked immunosorbent assay. STAR Protoc. 2024 Dec 20; 5(4):103402. View Abstract
  2. An ionic liquid-based adjuvant for modulating cellular and humoral immune responses. J Control Release. 2024 Dec; 376:632-645. View Abstract
  3. The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo. iScience. 2024 Nov 15; 27(11):111055. View Abstract
  4. Social complexity of a fentanyl vaccine to prevent opioid overdose conference proceedings: Radcliffe Institute for Advanced Study conference proceedings. Vaccine. 2025 Jan 12; 44:126324. View Abstract
  5. Adjuvantation of a SARS-CoV-2 mRNA vaccine with controlled tissue-specific expression of an mRNA encoding IL-12p70. Sci Transl Med. 2024 Jul 24; 16(757):eadm8451. View Abstract
  6. Need for strategic communications and stakeholder engagement to advance acceptability of an overdose preventing vaccine targeting fentanyl. Vaccine. 2024 Oct 24; 42(24):126082. View Abstract
  7. From hit to vial: Precision discovery and development of an imidazopyrimidine TLR7/8 agonist adjuvant formulation. Sci Adv. 2024 Jul 05; 10(27):eadg3747. View Abstract
  8. BECC-engineered live-attenuated Shigella vaccine candidates display reduced endotoxicity with robust immunogenicity in mice. Res Sq. 2024 Jun 11. View Abstract
  9. Immune profiling of age and adjuvant-specific activation of human blood mononuclear cells in vitro. Commun Biol. 2024 06 08; 7(1):709. View Abstract
  10. Human in vitro modeling of adjuvant formulations demonstrates enhancement of immune responses to SARS-CoV-2 antigen. NPJ Vaccines. 2023 Oct 26; 8(1):163. View Abstract
  11. Reduced SARS-CoV-2 mRNA vaccine immunogenicity and protection in mice with diet-induced obesity and insulin resistance. J Allergy Clin Immunol. 2023 11; 152(5):1107-1120.e6. View Abstract
  12. A protocol for high-throughput screening for immunomodulatory compounds using human primary cells. STAR Protoc. 2023 Sep 15; 4(3):102405. View Abstract
  13. Precision Vaccinology Approaches for the Development of Adjuvanted Vaccines Targeted to Distinct Vulnerable Populations. Pharmaceutics. 2023 Jun 19; 15(6). View Abstract
  14. Publisher Correction: Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice. NPJ Vaccines. 2023 Mar 03; 8(1):30. View Abstract
  15. Carbohydrate fatty acid monosulphate: oil-in-water adjuvant enhances SARS-CoV-2 RBD nanoparticle-induced immunogenicity and protection in mice. NPJ Vaccines. 2023 Feb 14; 8(1):18. View Abstract
  16. The mRNA vaccine BNT162b2 demonstrates impaired TH1 immunogenicity in human elders in vitro and aged mice in vivo. Res Sq. 2022 Dec 21. View Abstract
  17. Reduced SARS-CoV-2 mRNA vaccine immunogenicity and protection in mice with diet-induced obesity and insulin resistance. bioRxiv. 2022 Dec 07. View Abstract
  18. Development of a TLR7/8 agonist adjuvant formulation to overcome early life hyporesponsiveness to DTaP vaccination. Sci Rep. 2022 10 18; 12(1):16860. View Abstract
  19. Shaping Neonatal Immunization by Tuning the Delivery of Synergistic Adjuvants via Nanocarriers. ACS Chem Biol. 2022 09 16; 17(9):2559-2571. View Abstract
  20. Precision Vaccine Adjuvants for Older Adults: A Scoping Review. Clin Infect Dis. 2022 08 15; 75(Suppl 1):S72-S80. View Abstract
  21. A Precision Adjuvant Approach to Enhance Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccines Optimized for Immunologically Distinct Vulnerable Populations. Clin Infect Dis. 2022 08 15; 75(Suppl 1):S30-S36. View Abstract
  22. Acceptability of a Fentanyl Vaccine to Prevent Opioid Overdose and Need for Personalized Decision-Making. Clin Infect Dis. 2022 08 15; 75(Suppl 1):S98-S109. View Abstract
  23. mRNA booster vaccination protects aged mice against the SARS-CoV-2 Omicron variant. Commun Biol. 2022 08 06; 5(1):790. View Abstract
  24. Adjuvant Discovery via a High Throughput Screen using Human Primary Mononuclear Cells. bioRxiv. 2022 Jul 11. View Abstract
  25. An adjuvant strategy enabled by modulation of the physical properties of microbial ligands expands antigen immunogenicity. Cell. 2022 02 17; 185(4):614-629.e21. View Abstract
  26. Precision Vaccine Development: Cues From Natural Immunity. Front Immunol. 2021; 12:662218. View Abstract
  27. An aluminum hydroxide:CpG adjuvant enhances protection elicited by a SARS-CoV-2 receptor binding domain vaccine in aged mice. Sci Transl Med. 2022 Jan 26; 14(629):eabj5305. View Abstract
  28. Alum:CpG adjuvant enables SARS-CoV-2 RBD-induced protection in aged mice and synergistic activation of human elder type 1 immunity. bioRxiv. 2021 May 21. View Abstract
  29. Neonatal monocytes demonstrate impaired homeostatic extravasation into a microphysiological human vascular model. Sci Rep. 2020 10 20; 10(1):17836. View Abstract
  30. Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference. Front Immunol. 2020; 11:590373. View Abstract
  31. The sixth revolution in pediatric vaccinology: immunoengineering and delivery systems. Pediatr Res. 2021 05; 89(6):1364-1372. View Abstract
  32. BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny. Front Microbiol. 2020; 11:332. View Abstract
  33. The TLR5 Agonist Flagellin Shapes Phenotypical and Functional Activation of Lung Mucosal Antigen Presenting Cells in Neonatal Mice. Front Immunol. 2020; 11:171. View Abstract
  34. Toward precision adjuvants: optimizing science and safety. Curr Opin Pediatr. 2020 02; 32(1):125-138. View Abstract
  35. 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 12; 62(12). View Abstract
  36. 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. 2019 01 03; 37(1):80-89. View Abstract
  37. Recent Advances in the Discovery and Delivery of TLR7/8 Agonists as Vaccine Adjuvants. Immunohorizons. 2018 07 02; 2(6):185-197. View Abstract
  38. 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
  39. Adjuvant Effect of Bacille Calmette-Guérin on Hepatitis B Vaccine Immunogenicity in the Preterm and Term Newborn. Front Immunol. 2018; 9:29. View Abstract
  40. Identification and Characterization of Stimulator of Interferon Genes As a Robust Adjuvant Target for Early Life Immunization. Front Immunol. 2017; 8:1772. View Abstract
  41. 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
  42. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight. 2017 03 23; 2(6):e91020. View Abstract
  43. 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
  44. A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity. Front Immunol. 2016; 7:562. View Abstract
  45. 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
  46. Early life immune ontogeny - understanding how we build and sustain immunity to infection. Perspect Public Health. 2016 Jul; 136(4):205-7. View Abstract
  47. Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells. Innate Immun. 2016 08; 22(6):433-43. View Abstract
  48. 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
  49. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures. Mol Cell Proteomics. 2016 06; 15(6):1877-94. View Abstract
  50. Pediatric Vaccine Adjuvants: Components of the Modern Vaccinologist's Toolbox. Pediatr Infect Dis J. 2015 Dec; 34(12):1395-8. View Abstract
  51. 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
  52. 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
  53. Ontogeny of early life immunity. Trends Immunol. 2014 Jul; 35(7):299-310. View Abstract
  54. The effects of Fasciola hepatica tegumental antigens on mast cell function. Int J Parasitol. 2013 Jun; 43(7):531-9. View Abstract
  55. The ultra-potent and selective TLR8 agonist VTX-294 activates human newborn and adult leukocytes. PLoS One. 2013; 8(3):e58164. View Abstract
  56. Plasma cytokines, chemokines and cellular immune responses in pre-school Nigerian children infected with Plasmodium falciparum. Malar J. 2013 Jan 07; 12:5. View Abstract
  57. Identification of the major proteins of an immune modulating fraction from adult Fasciola hepatica released by Nonidet P40. Vet Parasitol. 2013 Jan 31; 191(3-4):379-85. View Abstract
  58. The Sigma class glutathione transferase from the liver fluke Fasciola hepatica. PLoS Negl Trop Dis. 2012; 6(5):e1666. View Abstract
  59. 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
  60. Ascaris lumbricoides pseudocoelomic body fluid induces a partially activated dendritic cell phenotype with Th2 promoting ability in vivo. Int J Parasitol. 2011 Feb; 41(2):255-61. View Abstract
  61. Major secretory antigens of the helminth Fasciola hepatica activate a suppressive dendritic cell phenotype that attenuates Th17 cells but fails to activate Th2 immune responses. Infect Immun. 2010 Feb; 78(2):793-801. View Abstract
  62. The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function. Infect Immun. 2009 Jun; 77(6):2488-98. View Abstract
  63. A comparative analysis of cytokine responses, cell surface marker expression and MAPKs in DCs matured with LPS compared with a panel of TLR ligands. Cytokine. 2008 Mar; 41(3):254-62. View Abstract

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