Positions

Selected Publications

Academic Article

Year Title Altmetric
2019 Common variable immunodeficiency patients display elevated plasma levels of granulocyte activation markers elastase and myeloperoxidaseInternational Journal of Immunopathology and Pharmacology.  33. 2019
2019 Neutrophil and granulocytic myeloid-derived suppressor cell-mediated t cell suppression significantly contributes to immune dysregulation in common variable immunodeficiency disordersJournal of Immunology.  202:93-104. 2019
2018 Is a lower-dose, subcutaneous contraceptive injectable containing depot medroxyprogesterone acetate likely to impact women's risk of HIV?Contraception.  97:191-197. 2018
2018 Hormonal contraception and HIV-1 acquisition: Biological mechanismsRecent Progress in Hormone Research.  39:36-78. 2018
2017 Dysregulation of Systemic and Mucosal Humoral Responses to Microbial and Food Antigens as a Factor Contributing to Microbial Translocation and Chronic Inflammation in HIV-1 InfectionPLoS Pathogens.  13. 2017
2016 Erratum: Corrigendum to “Effect of progestins on immunity: medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCs” (Contraception (2014) 90(2) (123–129) (S0010782414000535) (10.1016/j.contraception.2014.02.006))Contraception.  94:578. 2016
2015 Effect of hormonal contraception on the function of plasmacytoid dendritic cells and distribution of immune cell populations in the female reproductive tractJournal of Acquired Immune Deficiency Syndromes and Human Retrovirology.  68:511-518. 2015
2014 Altered Serum Cytokine Signature in Common Variable ImmunodeficiencyJournal of Clinical Immunology.  34:971-978. 2014
2014 Effect of progestins on immunity: Medroxyprogesterone but not norethisterone or levonorgestrel suppresses the function of T cells and pDCsContraception.  90:123-129. 2014
2014 Immune Suppression by Neutrophils in HIV-1 Infection: Role of PD-L1/PD-1 PathwayPLoS Pathogens.  10. 2014
2013 The Neonatal Fc Receptor (FcRn) Enhances Human Immunodeficiency Virus Type 1 (HIV-1) Transcytosis across Epithelial CellsPLoS Pathogens.  9. 2013
2013 Hormonal contraception and hiv-1 infection: Medroxyprogesterone acetate suppresses innate and adaptive immune mechanismsEndocrinology.  154:1282-1295. 2013
2013 Optimization of the transductional efficiency of lentiviral vectors: Effect of sera and polycationsMolecular Biotechnology.  53:308-314. 2013
2012 Chronic immune activation in common variable immunodeficiency (CVID) is associated with elevated serum levels of soluble CD14 and CD25 but not endotoxaemiaClinical and Experimental Immunology.  170:321-332. 2012
2011 Menstrual blood as a potential source of endometrial derived CD3+ T cellsPLoS ONE.  6. 2011
2011 Limited transplantation of antigen-expressing hematopoietic stem cells induces long-lasting cytotoxic T cell responsesPLoS ONE.  6. 2011
2010 Sex steroid hormones, hormonal contraception, and the immunobiology of human immunodeficiency virus-1 infectionRecent Progress in Hormone Research.  31:79-97. 2010
2009 Induction of protective cytotoxic T-cell responses by a B-cell-based cellular vaccine requires stable expression of antigenGene Therapy.  16:1300-1313. 2009
2009 A model for testing the immunogenicity of simian immunodeficiency virus and simian-human immunodeficiency virus vaccine candidates in miceJournal of Virological Methods.  158:70-76. 2009
2009 Mucosal immunology of the genital and gastrointestinal tracts and HIV-1 infectionJournal of Reproductive Immunology.  83:196-200. 2009
2008 Delivery of DNA HIV-1 vaccine to the liver induces high and long-lasting humoral immune responsesVaccine.  26:1541-1551. 2008
2006 HIV infection: first battle decides the warImmunology Today.  27:274-281. 2006
2006 Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4 + T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIV KU2 RNA levelsJournal of Virology.  80:3732-3742. 2006
2006 Improved vaccine protection from simian AIDS by the addition of nonstructural simian immunodeficiency virus genesJournal of Immunology.  176:85-96. 2006
2005 Fragile X-related protein FXR1P regulates proinflammatory cytokine tumor necrosis factor expression at the post-transcriptional levelJournal of Biological Chemistry.  280:5750-5763. 2005
2002 Immune intervention strategies for HIV-1 infection of humans in the SIV macaque modelVaccine.  20. 2002
2002 Containment of simian immunodeficiency virus infection in vaccinated macaques: Correlation with the magnitude of virus-specific pre- and postchallenge CD4+ and CD8+ T cell responsesJournal of Immunology.  169:4778-4787. 2002
2002 Vaccination of macaques with long-standing SIVmac251 infection lowers the viral set point after cessation of antiretroviral therapyJournal of Immunology.  169:5347-5357. 2002
2002 A novel chimeric Rev, Tat, and Nef (Retanef) antigen as a component of an SIV/HIV vaccineVaccine.  20:3171-3186. 2002
2002 ALVAC-SIV-gag-pol-env-based vaccination and macaque major histocompatibility complex class I (A*01) delay simian immunodeficiency virus SIVmac-induced immunodeficiencyJournal of Virology.  76:292-302. 2002
2002 Cervicovaginal lamina propria lymphocytes: Phenotypic characterization and their importance in cytotoxic T-lymphocyte responses to simian immunodeficiency virus SIVmac251Journal of Virology.  76:9-18. 2002
2002 Design and in vivo immunogenicity of a polyvalent vaccine based on SIVmac regulatory genesDNA (Mary Ann Liebert, Inc.).  21:619-626. 2002
2002 Equivalent immunogenicity of the highly attenuated poxvirus-based ALVAC-SIV and NYVAC-SIV vaccine candidates in SIVmac251-infected macaquesVirology.  304:125-134. 2002
2001 Potentiation of Simian Immunodeficiency Virus (SIV)-specific CD4+ and CD8+ T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimenJournal of Immunology.  167:7180-7191. 2001
2001 Towards an improved AIDS vaccine: Enhancing the MHC class I and II antigen presentation of SIV proteins using ubiquitin and HLA-DM targeting sequencesMcgill Journal of Medicine.  6:4-7. 2001
2001 Impairment of Gag-specific CD8+ T-cell function in mucosal and systemic compartments of simian immunodeficiency virus mac251- and simian-human immunodeficiency virus KU2-infected macaquesJournal of Virology.  75:11483-11495. 2001
2001 Differences in time of virus appearance in the blood and virus-specific immune responses in intravenous and intrarectal primary SIVmac251 infection of rhesus macaques; A pilot studyBMC Infectious Diseases.  1. 2001
2001 Polymorphism in the 3′-untranslated region of TNFα mRNA impairs binding of the post-transcriptional regulatory protein HuR to TNFα mRNANucleic Acids Research.  29:863-871. 2001
2001 Mucosal AIDS vaccine reduces disease and viral load in gut reservoir and blood after mucosal infection of macaquesNature Medicine.  7:1320-1326. 2001
2000 Viremia control following antiretroviral treatment and therapeutic immunization during primary SIV251 infection of macaquesNature Medicine.  6:1140-1146. 2000
1998 Characterization of the RNA binding proteins forming complexes with a novel putative regulatory region in the 3'-UTR of TNF-α mRNANucleic Acids Research.  26:2803-2812. 1998
1998 Phenotypic difference between Bcg(r) and Bcg(s) macrophages is related to differences in protein-kinase-C-dependent signallingEuropean Journal of Biochemistry.  251:734-743. 1998
1996 Two distinct regions in the 3' untranslated region of tumor necrosis factor alpha mRNA form complexes with macrophage proteinsMolecular and Cellular Biology.  16:5579-5590. 1996

Research Overview

  • Research in our laboratory focuses on the following areas: 1) The multifaceted role of neutrophils in HIV-1-infection. In recent years, a new appreciation of the role of neutrophils in regulating the immune system has emerged. Neutrophils are the most abundant leukocyte population and are traditionally recognized as essential effector cells of the innate immune system in the host defense against invading organisms. While neutrophils have been shown to play important roles in viral pathogenesis, a knowledge gap exists in our understanding of the function of neutrophils in individuals infected with human immunodeficiency virus-1 (HIV-1). The data recently accumulated in our laboratory reveals the multifaceted role of neutrophils in HIV-1-infection where they exert both pro-inflammatory and anti-inflammatory effects. We demonstrated that chronic HIV-1-infection and ongoing microbial translocation is associated with the induction of neutrophils with immunosuppressive activity that significantly contribute to the suppression of T cell function in HIV-1-infection. In addition, we show that enhanced neutrophil extracellular trap (NET) formation in HIV-1-infected subjects may contribute to the incidence of inflammatory-driven disease through direct effects of NETs or indirectly through NET mediated effects on macrophage function. These findings show that the role of neutrophils in HIV-1-infection is more complex than previously recognized. 2) Mucosal antibody production and the pathogenesis of HIV-1 infection. The decline of CD4+ T cells, a hallmark of HIV-1 infection and indicator of disease progression, is caused primarily by chronic activation of immune system; however, the underlying causes of this activation remain unclear. We hypothesize that HIV-1 infection is associated with a severe reduction of IgA responses to common microbial and food antigens proportionally to the extent of CD4+ T cell depletion and polyclonal activation of IgA-producing B cells at mucosal tissues. We investigate whether the inability to mount specific IgA responses results in increased absorption of environmental antigens to the systemic compartment contributing to the chronic activation of CD4+ and CD8+ T cells characteristic for HIV-1 infection. 3) Effect of sex steroid hormones and hormonal contraception on the immunobiology of HIV-1 infection. Worldwide, increasing number of women uses oral or injectable hormonal contraceptives. However, inadequate information is available to aid women and healthcare professionals in weighing the potential risks of hormonal contraceptive use in individuals living with human immunodeficiency virus-1 (HIV-1) or at high risk of infection. Numerous epidemiological studies suggest that progesterone-based contraceptives increase the risk of HIV-1 infection in humans, accelerate disease progression, and increase viral shedding in the genital tract. In contrast to progesterone, systemic or intravaginal treatment with estrogen efficiently protects female rhesus macaques against the transmission of SIV, likely by enhancing the natural protective properties of the lower genital tract mucosal tissue. We investigate the effect of progesterone, medroxyprogesterone, and estrogen on various immune functions in HIV-1-infected women and uninfected controls. 4) HIV-1 vaccine development. SIV infection in macaques closely resembles human AIDS and represents the best model for assessing the protective efficacy of candidate HIV-1 vaccine. Previously, we demonstrated that immunization with an attenuated recombinant poxvirus vector NYVAC-SIV in combination with a DNA-SIV vaccine candidate expressing the structural genes of SIV resulted in high levels of virus-specific CD4+ and CD8+ T-cell responses and in a significant suppression of viremia following an exposure to the highly pathogenic SIV virus. In addition, we showed a significant improvement following an addition of early/auxiliary genes rev, tat, and nef to the vaccine. Currently, we are developing and testing new vaccine strategies. 5) Design of novel strategies for the immunotherapy of cancer. Immunization of patients with tumor-associated antigens results in the induction of tumor-specific immune responses that can significantly restrict or eliminate the spreading tumor. We are testing the possibility of transplantation with genetically modified hematopoietic stem cells (HSCs) targeting the expression of antigen to activated dendritic cells as a strategy for long-term cancer immunotherapy. In a second project, we investigate immunization with antigen-presenting genetically modified B cells specifically targeted to secondary lymphoid tissue.
  • Education And Training

  • Doctor of Philosophy Level Degree in Medicine, McGill University 1997
  • Master's Level Degree in Medical Biochemistry, Charles University in Prague 1990
  • Full Name

  • Zdenek Hel