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.

MEDICAL SERVICES

Languages

  • English

Researcher Services

Researcher Areas

  • Molecular mechanism of vaccine adjuvants
  • Vaccine Development

Research Divisions

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Strunk T, van Haren SD, Hibbert J, Pettengill M, Ozonoff A, Jans J, Schüller SS, Burgner D, Levy O, Currie AJ. 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. 2019 Oct 02. View abstract
  2. Lee AH, Shannon CP, Amenyogbe N, Bennike TB, Diray-Arce J, Idoko OT, Gill EE, Ben-Othman R, Pomat WS, van Haren SD, Cao KL, Cox M, Darboe A, Falsafi R, Ferrari D, Harbeson DJ, He D, Bing C, Hinshaw SJ, Ndure J, Njie-Jobe J, Pettengill MA, Richmond PC, Ford R, Saleu G, Masiria G, Matlam JP, Kirarock W, Roberts E, Malek M, Sanchez-Schmitz G, Singh A, Angelidou A, Smolen KK, Brinkman RR, Ozonoff A, Hancock REW, van den Biggelaar AHJ, Steen H, Tebbutt SJ, Kampmann B, Levy O, Kollmann TR. 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
  3. 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
  4. 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 03 23; 2(6):e91020. View abstract
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. Pettengill MA, van Haren SD, Levy O. Soluble mediators regulating immunity in early life. Front Immunol. 2014; 5:457. View abstract
  12. van Haren SD, Wroblewska A, Herczenik E, Kaijen PH, Ruminska A, ten Brinke A, Meijer AB, Voorberg J. Limited promiscuity of HLA-DRB1 presented peptides derived of blood coagulation factor VIII. PLoS One. 2013; 8(11):e80239. View abstract
  13. Sorvillo N, van Haren SD, Kaijen PH, ten Brinke A, Fijnheer R, Meijer AB, Voorberg J. 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
  14. Wroblewska A, van Haren SD, Herczenik E, Kaijen P, Ruminska A, Jin SY, Zheng XL, van den Biggelaar M, ten Brinke A, Meijer AB, Voorberg J. 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
  15. van Haren SD, Wroblewska A, Fischer K, Voorberg J, Herczenik E. Requirements for immune recognition and processing of factor VIII by antigen-presenting cells. Blood Rev. 2012 Jan; 26(1):43-9. View abstract
  16. Herczenik E, van Haren SD, Wroblewska A, Kaijen P, van den Biggelaar M, Meijer AB, Martinez-Pomares L, ten Brinke A, Voorberg J. 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
  17. van Haren SD, Herczenik E, ten Brinke A, Mertens K, Voorberg J, Meijer AB. 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
  18. James EA, van Haren SD, Ettinger RA, Fijnvandraat K, Liberman JA, Kwok WW, Voorberg J, Pratt KP. 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
  19. Williams CP, Schueller N, Thompson CA, van den Berg M, Van Haren SD, Erdmann R, Bond CS, Distel B, Schliebs W, Wilmanns M, Stanley WA. 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
  20. van Haren SD, Voorberg J. Getting rid of bad memory. Blood. 2011 Jan 06; 117(1):7-8. View abstract
  21. van Helden PM, Van Haren SD, Fijnvandraat K, van den Berg HM, Voorberg J. Factor VIII-specific B cell responses in haemophilia A patients with inhibitors. Haemophilia. 2010 May; 16(102):35-43. View abstract
  22. Diehl SA, Schmidlin H, Nagasawa M, van Haren SD, Kwakkenbos MJ, Yasuda E, Beaumont T, Scheeren FA, Spits H. 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