ABOUT THE RESEARCHER

OVERVIEW

Simon van Haren’s research is focused on better understanding the molecular basis of age-specific immune responses to vaccines. Understanding how the human immune system changes with age in how it responds to vaccination can ultimately inform the development of novel vaccines to provide early life protection against pathogens such as Respiratory Syncytial Virus (RSV).

  • A major area of his research is to dissect the molecular mechanism of adjuvant synergy. Adjuvants are key vaccine components capable of instructing different types of immune responses. Supported by an Early Career Award from the Thrasher Research Fund, he completed a project that aims to identify combinations of Toll-like receptor (TLR) and C-type lectin receptor (CLR) agonists that could overcome the classical impairment in CD4+ T cell-polarization seen in newborns. This study has identified novel age-dependent synergy between specific TLR and CLR adjuvant combinations, which are currently under evaluation for their ability to enhance early life immunity against RSV.
  • The second major area of Dr. van Haren’s research is the study of antigen presentation and the effect of vaccine adjuvants on this process. Dr. van Haren has developed a portfolio of mass-spectrometry techniques and cell culture platforms that can be used to study the ability of vaccine adjuvants, or combinations, to enhance the presentation of vaccine antigens on MHC class II or to induce antigen cross-presentation on MHC class I. The ability to induce cross-presentation and subsequently induce a CD8+ T cell response is key for developing immunity against intracellular pathogens such as RSV or Influenza.

Dr. van Haren has modeled the immune systems of newborns, 6-month old infants, adults, and elderly individuals in different in vitro settings, such as whole blood, monocytes, monocyte-derived DCs, B-and T-cells and a microphysiological tissue construct. Using state-of-the-art mass-spectrometry and cell biology techniques he aims to unravel the ontogeny of the human immune response to vaccines at the molecular level, with the goal to provide novel insights relevant to future vaccine development.

BACKGROUND

Simon van Haren obtained his Ph.D at Utrecht University in The Netherlands, where he conducted immunological and biochemical research studying the formation of Factor VIII-neutralizing antibodies in patients with hemophilia A. His research project was focused on the mechanism of endocytosis of Factor VIII by human dendritic cells, the presentation of antigenic peptides on MHC class II and the identification of antigen-specific CD4+ T cells.

He undertook postdoctoral training in the lab of Dr. Ofer Levy in the Division of Infectious Diseases at Boston Children’s Hospital.

PUBLICATIONS

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  1. Human Blood Plasma Shapes Distinct Neonatal TLR-Mediated Dendritic Cell Activation via Expression of the MicroRNA Let-7g. Immunohorizons. 2021 Apr 30; 5(4):246-256. View abstract
  2. Vaccine-Induced CD8+ T Cell Responses in Children: A Review of Age-Specific Molecular Determinants Contributing to Antigen Cross-Presentation. Front Immunol. 2020; 11:607977. View abstract
  3. Corrigendum: Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea. Front Pediatr. 2020; 8:610461. View abstract
  4. Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life. Front Immunol. 2020; 11:578505. View abstract
  5. Towards Precision Vaccines: Lessons From the Second International Precision Vaccines Conference. Front Immunol. 2020; 11:590373. View abstract
  6. Clinical Protocol for a Longitudinal Cohort Study Employing Systems Biology to Identify Markers of Vaccine Immunogenicity in Newborn Infants in The Gambia and Papua New Guinea. Front Pediatr. 2020; 8:197. View abstract
  7. 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
  8. Licensed Bacille Calmette-Guérin (BCG) formulations differ markedly in bacterial viability, RNA content and innate immune activation. Vaccine. 2020 02 24; 38(9):2229-2240. View abstract
  9. Cyclic AMP in human preterm infant blood is associated with increased TLR-mediated production of acute-phase and anti-inflammatory cytokines in vitro. Pediatr Res. 2020 11; 88(5):717-725. View abstract
  10. Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nat Commun. 2019 03 12; 10(1):1092. View abstract
  11. First International Precision Vaccines Conference: Multidisciplinary Approaches to Next-Generation Vaccines. mSphere. 2018 08 01; 3(4). View abstract
  12. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight. 2017 03 23; 2(6):e91020. View abstract
  13. 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
  14. A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation from Immunogenicity. Front Immunol. 2016; 7:562. View abstract
  15. 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
  16. Distinct TLR-mediated cytokine production and immunoglobulin secretion in human newborn naïve B cells. Innate Immun. 2016 08; 22(6):433-43. View abstract
  17. 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
  18. 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
  19. Soluble mediators regulating immunity in early life. Front Immunol. 2014; 5:457. View abstract
  20. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII. PLoS One. 2013; 8(11):e80239. View abstract
  21. Preferential HLA-DRB1*11-dependent presentation of CUB2-derived peptides by ADAMTS13-pulsed dendritic cells. Blood. 2013 Apr 25; 121(17):3502-10. View abstract
  22. Modification of an exposed loop in the C1 domain reduces immune responses to factor VIII in hemophilia A mice. Blood. 2012 May 31; 119(22):5294-300. View abstract
  23. Requirements for immune recognition and processing of factor VIII by antigen-presenting cells. Blood Rev. 2012 Jan; 26(1):43-9. View abstract
  24. Uptake of blood coagulation factor VIII by dendritic cells is mediated via its C1 domain. J Allergy Clin Immunol. 2012 Feb; 129(2):501-9, 509.e1-5. View abstract
  25. HLA-DR-presented peptide repertoires derived from human monocyte-derived dendritic cells pulsed with blood coagulation factor VIII. Mol Cell Proteomics. 2011 Jun; 10(6):M110.002246. View abstract
  26. T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site. J Thromb Haemost. 2011 Apr; 9(4):689-99. View abstract
  27. The Peroxisomal Targeting Signal 1 in sterol carrier protein 2 is autonomous and essential for receptor recognition. BMC Biochem. 2011 Mar 04; 12:12. View abstract
  28. Getting rid of bad memory. Blood. 2011 Jan 06; 117(1):7-8. View abstract
  29. Factor VIII-specific B cell responses in haemophilia A patients with inhibitors. Haemophilia. 2010 May; 16(102):35-43. View abstract
  30. STAT3-mediated up-regulation of BLIMP1 Is coordinated with BCL6 down-regulation to control human plasma cell differentiation. J Immunol. 2008 Apr 01; 180(7):4805-15. View abstract