About

Dr. Harm HogenEsch is a Distinguished Professor of Immunopathology in the Department of Comparative Pathobiology at the College of Veterinary Medicine, Purdue University. He grew up in the Netherlands and earned his Doctor of Veterinary Medicine (DVM) degree cum laude from the University of Utrecht in 1984. He pursued graduate training in immunology at the University of Illinois at Urbana-Champaign under the mentorship of Dr. Peter Felsburg, receiving his PhD in 1989. Dr. HogenEsch is board-certified by the American College of Veterinary Pathologists since 1989. After working as a staff scientist at the TNO Institute for Aging and Vascular Research in Leiden, the Netherlands, he joined Purdue University in 1993 and was promoted to Professor in 2001. Dr. HogenEsch has made significant contributions to veterinary immunopathology, with over 140 peer-reviewed journal articles and 18 book chapters published. He has trained 18 graduate students and postdoctoral fellows, reflecting his commitment to education and research mentorship. His research group focuses on vaccine development and adjuvants, as well as immunological mechanisms related to diseases such as atopic dermatitis. His work advances understanding of immune responses and the design of vaccines, contributing to both veterinary and translational immunology.

Research topics

• Biology
• Immunology
• Medicine
• Internal medicine
• Virology
• Materials science
• Biochemical engineering
• Engineering
• Biochemistry
• Nanotechnology
• Bioinformatics
• Computational biology
• Chemistry
• Microbiology

Selected publications

• A Chlamydia trachomatis CPAF-STING agonist conjugate vaccine administered intramuscularly and intradermally is immunogenic in the pig model

  UNC Libraries · 2026-05-05

  articleOpen access

  IntroductionChlamydia trachomatis (Ct) is the most common bacterial cause of sexually transmitted infection worldwide. Given the limited effectiveness of current Ct screening and treatment programs, alongside the lack of lasting immunity from natural infection, developing an effective vaccine is crucial. Pigs serve as a valuable model for chlamydia research due to their physiological similarity to humans and natural susceptibility to Chlamydia suis (Cs), a close relative of Ct. Thus, we utilized the pig model to evaluate the immunogenicity of three Chlamydial Protease-like Activity Factor (CPAF)-based vaccine candidates. Because stimulator of interferon genes (STING) pathway agonists have shown promise as adjuvants for subunit vaccines but are limited by rapid diffusion from the injection site and poor cellular uptake, we evaluated two improved STING agonist formulations: direct conjugation of the agonist to CPAF (CPAF-STG1151) and adsorption onto phytoglycogen nanoparticles (CPAF/NanoST), and compared their performance to a conventional oil-in-water microemulsion adjuvant (CPAF/IMS1313).MethodsPigs received two intramuscular (IM) or two intradermal (ID) doses and adaptive immune responses were assessed weekly by three-color FluoroSpot assays, multi-parameter flow cytometry and anti-CPAF ELISAs.ResultsAmong the vaccine candidates tested, the novel CPAF-STG1151 conjugate elicited the strongest systemic T cell response. It induced a robust cell-mediated immune response characterized by IFNγ production with or without TNFα coproduction and this response was equally mediated by all T cell subsets (CD4, CD8 and γδ T cells). The route of administration (IM vs. ID) had no significant effect on either the magnitude or the cytokine profile of the cell-mediated immune response. The highest anti-CPAF IgG serum levels were also observed following vaccination with the CPAF-STG1151 conjugate vaccine candidate.DiscussionThus, conjugation of the STING pathway agonist STG1151 to the Chlamydia protein CPAF resulted in a highly immunogenic subunit vaccine. Future studies will determine mucosal administration routes and assess the vaccine efficacy of this promising Ct vaccine candidate.

  PublisherDOI

• Aluminum adjuvants differentially induce IL-1β release in vitro yet share NLRP3 inflammasome-independent adjuvant effects in vivo

  Scientific Reports · 2026-01-10

  articleOpen accessSenior authorCorresponding

  Aluminum adjuvants are the most common adjuvants in human vaccines. The two types of aluminum adjuvants, aluminum hydroxide adjuvant (AH) and aluminum phosphate adjuvant (AP), differ in physical and chemical characteristics, but little is known about possible biological differences. While previous work demonstrated that AH and AP induce the secretion of IL-1β in an NLRP3-dependent manner, the role of NLRP3 in the stimulation of the immune response by aluminum adjuvants is controversial. Here, we report that AP induces more IL-1β in human and mouse macrophages and dendritic cells than AH. This effect is caused by increased NLRP3-dependent proteolysis of pro-IL-1β. In addition, AP caused a greater degree of cell damage than AH, resulting in the release of lactate dehydrogenase (LDH) and pro-IL-1β. The cell damage caused by aluminum adjuvants was partially dependent on NLRP3, suggesting that pyroptosis and other mechanisms of cell death are involved. In spite of these differences in NLRP3-dependent production of IL-1β, the ability of both aluminum adjuvants to enhance the antibody response in two different mouse models was not affected by deletion or inhibition of NLRP3. These results support the concept that aluminum adjuvants elicit redundant innate immune mechanisms that result in an enhanced adaptive immune response.

  PublisherOA PDFDOI

• A Chlamydia trachomatis CPAF-STING agonist conjugate vaccine administered intramuscularly and intradermally is immunogenic in the pig model

  Frontiers in Immunology · 2026-05-01

  articleOpen access

  Introduction Chlamydia trachomatis ( Ct ) is the most common bacterial cause of sexually transmitted infection worldwide. Given the limited effectiveness of current Ct screening and treatment programs, alongside the lack of lasting immunity from natural infection, developing an effective vaccine is crucial. Pigs serve as a valuable model for chlamydia research due to their physiological similarity to humans and natural susceptibility to Chlamydia suis ( Cs ), a close relative of Ct . Thus, we utilized the pig model to evaluate the immunogenicity of three Chlamydial Protease-like Activity Factor (CPAF)-based vaccine candidates. Because stimulator of interferon genes (STING) pathway agonists have shown promise as adjuvants for subunit vaccines but are limited by rapid diffusion from the injection site and poor cellular uptake, we evaluated two improved STING agonist formulations: direct conjugation of the agonist to CPAF (CPAF-STG1151) and adsorption onto phytoglycogen nanoparticles (CPAF/NanoST), and compared their performance to a conventional oil-in-water microemulsion adjuvant (CPAF/IMS1313). Methods Pigs received two intramuscular (IM) or two intradermal (ID) doses and adaptive immune responses were assessed weekly by three-color FluoroSpot assays, multi-parameter flow cytometry and anti-CPAF ELISAs. Results Among the vaccine candidates tested, the novel CPAF-STG1151 conjugate elicited the strongest systemic T cell response. It induced a robust cell-mediated immune response characterized by IFNγ production with or without TNFα coproduction and this response was equally mediated by all T cell subsets (CD4, CD8 and γδ T cells). The route of administration (IM vs. ID) had no significant effect on either the magnitude or the cytokine profile of the cell-mediated immune response. The highest anti-CPAF IgG serum levels were also observed following vaccination with the CPAF-STG1151 conjugate vaccine candidate. Discussion Thus, conjugation of the STING pathway agonist STG1151 to the Chlamydia protein CPAF resulted in a highly immunogenic subunit vaccine. Future studies will determine mucosal administration routes and assess the vaccine efficacy of this promising Ct vaccine candidate.

  PublisherDOI

• Role of adjuvants in the efficacy of an IZUMO1-based immunocontraceptive vaccine in mice

  Vaccine · 2025-12-06

  articleOpen accessSenior author

  The binding of the sperm protein IZUMO1 to the oocyte receptor JUNO is an essential step in fertilization. Genetic deletion of IZUMO1 results in sterility, making this sperm protein a potential target for the development of an immunocontraceptive vaccine for the control of wildlife populations. However, contradictory results of the effect of immunization with IZUMO1 or IZUMO1-derived peptides have been reported. In this study, the effect of immunization with a recombinant mouse IZUMO1 peptide comprised of the extracellular Izumo, hairpin and Ig-like domains of IZUMO1 with different adjuvants was investigated in mice. The adjuvants were AddaS03, the nanoparticle adjuvant NanoST, composed of α-D-glucan nanoparticles and the STING agonist ADU-S100, or a combination of these two adjuvants. Immunization of outbred female mice induced a robust anti-IZUMO1 IgG response with significantly higher serum IgG2a titers in mice immunized with NanoST compared with AddaS03. Vaccines with NanoST alone or in combination with AddaS03 reduced the pregnancy rate and number of pups by more than 50 %, whereas vaccines formulated with AddaS03 alone had a limited effect. Infertility correlated with IgG directed against epitopes in the hairpin region of IZUMO1. These results support the further development of IZUMO1-based immunocontraceptive vaccines for wildlife population control.

  PublisherDOI

• In-Situ Self-Assembling Oligomeric Collagen Scaffold Enhances Vaccine Retention and Vaccine-Induced Humoral Immunity

  Vaccines · 2025-11-08 · 1 citations

  articleOpen accessSenior authorCorresponding

  Background/Objectives: Subunit vaccines composed of purified proteins and adjuvants offer excellent safety, but often generate short-lived immunity due to rapid antigen clearance and limited antigen-presenting cell engagement. Sustained, localized delivery of antigen and adjuvant may improve the magnitude and durability of the immune response without compromising safety. This study evaluated an in-situ polymerizing type I oligomeric collagen (Oligomer) scaffold to localize antigen/adjuvant at the injection site and prolong antigen presentation. Methods: Mice were immunized intramuscularly with ovalbumin (OVA) and CpG oligonucleotide adjuvant delivered alone or co-formulated with Oligomer. Antibody response and inflammation at the injection site were assessed post-booster at early (Day 32) and late (Day 68) time points. Antigen retention and dendritic cell trafficking to draining lymph nodes were evaluated using fluorescently labeled OVA. Results: The Oligomer scaffold retained vaccine antigen at the injection site without eliciting a material-mediated foreign body response. Co-delivery of OVA and CpG within the scaffold enhanced germinal center activity, increased follicular helper T cells and germinal center B cells, and skewed CD4+ T cells toward a Th1 phenotype. Humoral responses were greater and more durable, with higher OVA-specific IgG, IgG1, and IgG2a titers and an increased number of bone marrow antibody-secreting cells persisting through Day 68. Antigen-positive dendritic cells, including both resident and migratory subsets, were elevated in draining lymph nodes, indicating enhanced antigen transport. No anti-mouse collagen I antibodies were detected, confirming the maintenance of collagen self-tolerance. Conclusions: The Oligomer delivery platform functioned as a localized, immunotolerant vaccine depot, sustaining antigen availability and immune cell engagement. This spatiotemporal control enhanced germinal center responses and generated a more robust, durable humoral immune response, supporting its potential to improve subunit vaccine efficacy while maintaining an excellent safety profile.

  PublisherOA PDFDOI

• Differences in the innate immune response between aluminum-based vaccine adjuvants 4319

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Aluminum hydroxide (AH) and aluminum phosphate (AP) are widely used vaccine adjuvants, yet their mechanisms of action remain poorly understood. The choice of these adjuvants is mainly guided by their physical and chemical properties, while little is known about potential functional differences. Here, we demonstrate that AP induced significantly higher IL-1β secretion than AH in human THP-1 macrophages and mouse bone marrow-derived macrophages (BMDMs) under LPS-primed conditions. Inhibition by MCC950 and the use of macrophages from NLRP3-deficient mice confirmed that IL-1β secretion induced by both adjuvants in vitro was dependent on the NLRP3 inflammasome. In vivo, AH and AP also showed different kinetics of innate immune cell recruitment, with AP inducing a higher number of neutrophils and dendritic cells at 96 hours after injection. These findings highlight biological differences between AH and AP, with distinct inflammatory profiles and kinetics of immune cell recruitment. In addition, the role of the NLRP3 inflammasome was examined in vivo to understand its role in driving immunostimulation by AH and AP. Both adjuvants elicited similar IgG and IgG1 responses in wild-type and NLRP3-deficient mice indicating that NLRP3 is not as critical to the immune response induced by aluminum-adjuvanted vaccines. Topic Categories Vaccines and Immunotherapy (VAC)

  PublisherOA PDFDOI

• Evaluation of Efficacy of Surface Coated versus Encapsulated Influenza Antigens in Mannose–Chitosan Nanoparticle-Based Intranasal Vaccine in Swine

  Vaccines · 2024-06-11 · 8 citations

  articleOpen access

  This study focuses on the development and characterization of an intranasal vaccine platform using adjuvanted nanoparticulate delivery of swine influenza A virus (SwIAV). The vaccine employed whole inactivated H1N2 SwIAV as an antigen and STING-agonist ADU-S100 as an adjuvant, with both surface adsorbed or encapsulated in mannose-chitosan nanoparticles (mChit-NPs). Optimization of mChit-NPs included evaluating size, zeta potential, and cytotoxicity, with a 1:9 mass ratio of antigen to NP demonstrating high loading efficacy and non-cytotoxic properties suitable for intranasal vaccination. In a heterologous H1N1 pig challenge trial, the mChit-NP intranasal vaccine induced cross-reactive sIgA antibodies in the respiratory tract, surpassing those of a commercial SwIAV vaccine. The encapsulated mChit-NP vaccine induced high virus-specific neutralizing antibody and robust cellular immune responses, while the adsorbed vaccine elicited specific high IgG and hemagglutinin inhibition antibodies. Importantly, both the mChit-NP vaccines reduced challenge heterologous viral replication in the nasal cavity higher than commercial swine influenza vaccine. In summary, a novel intranasal mChit-NP vaccine platform activated both the arms of the immune system and is a significant advancement in swine influenza vaccine design, demonstrating its potential effectiveness for pig immunization.

  PublisherOA PDFDOI

• Heritability and genome-wide association study of vaccine-induced immune response in Beagles: A pilot study

  Vaccine · 2024-04-01 · 4 citations

  articleOpen access

  Both genetic and non-genetic factors contribute to individual variation in the immune response to vaccination. Understanding how genetic background influences variation in both magnitude and persistence of vaccine-induced immunity is vital for improving vaccine development and identifying possible causes of vaccine failure. Dogs provide a relevant biomedical model for investigating mammalian vaccine genetics; canine breed structure and long linkage disequilibrium simplify genetic studies in this species compared to humans. The objective of this study was to estimate the heritability of the antibody response to vaccination against viral and bacterial pathogens, and to identify genes driving variation of the immune response to vaccination in Beagles. Sixty puppies were immunized following a standard vaccination schedule with an attenuated combination vaccine containing antigens for canine adenovirus type 2, canine distemper virus, canine parainfluenza virus, canine parvovirus, and four strains of Leptospira bacteria. Serum antibody measurements for each viral and bacterial component were measured at multiple time points. Heritability estimations and GWAS were conducted using SNP genotypes at 279,902 markers together with serum antibody titer phenotypes. The heritability estimates were: (1) to Leptospira antigens, ranging from 0.178 to 0.628; and (2) to viral antigens, ranging from 0.199 to 0.588. There was not a significant difference between overall heritability of vaccine-induced immune response to Leptospira antigens compared to viral antigens. Genetic architecture indicates that SNPs of low to high effect contribute to immune response to vaccination. GWAS identified two genetic markers associated with vaccine-induced immune response phenotypes. Collectively, these findings indicate that genetic regulation of the immune response to vaccination is antigen-specific and influenced by multiple genes of small effect.

  PublisherDOI

• Intradermal vaccination with a phytoglycogen nanoparticle and STING agonist induces cytotoxic T lymphocyte-mediated antitumor immunity

  npj Vaccines · 2024-08-17 · 4 citations

  articleOpen accessSenior author

  Abstract A critical aspect of cancer vaccine development is the formulation with effective adjuvants. This study evaluated whether combining a cationic plant-derived nanoparticle adjuvant (Nano-11) with the clinically tested STING agonist ADU-S100 (MIW815) could stimulate anticancer immunity by intradermal vaccination. Nano-11 combined with ADU-S100 (NanoST) synergistically activated antigen-presenting cells, facilitating protein antigen cross-presentation in vitro and in vivo. Intradermal vaccination using ovalbumin (OVA) as a tumor antigen and combined with Nano-11 or NanoST prevented the development of murine B16-OVA melanoma and E.G7-OVA lymphoma tumors. The antitumor immunity was abolished by CD8 + T cell depletion but not by CD4 + T cell depletion. Therapeutic vaccination with NanoST increased mouse survival by inhibiting B16-OVA tumor growth, and this effect was further enhanced by PD-1 checkpoint blockade. Our study provides a strong rationale for developing NanoST as an adjuvant for intradermal vaccination and next-generation preventative and therapeutic cancer vaccines by STING-targeted activation.

  PublisherOA PDFDOI

• Characterization of a novel functional porcine CD3+CD4lowCD8α+CD8β+ T-helper/memory lymphocyte subset in the respiratory tract lymphoid tissues of swine influenza A virus vaccinated pigs

  Veterinary Immunology and Immunopathology · 2024-06-05

  articleOpen access

  The pig is emerging as a physiologically relevant biomedical large animal model. Delineating the functional roles of porcine adaptive T-lymphocyte subsets in health and disease is of critical significance, which facilitates mechanistic understanding of antigen-specific immune memory responses. We identified a novel T-helper/memory lymphocyte subset in pigs and performed phenotypic and functional characterization of these cells under steady state and following vaccination and infection with swine influenza A virus (SwIAV). A novel subset of CD3 + CD4 low CD8α + CD8β + memory T-helper cells was identified in the blood of healthy adult pigs under homeostatic conditions. To understand the possible functional role/s of these cells, we characterized the antigen-specific T cell memory responses by multi-color flow cytometry in pigs vaccinated with a whole inactivated SwIAV vaccine, formulated with a phytoglycogen nanoparticle/STING agonist (ADU-S100) adjuvant (NanoS100-SwIAV). As a control, a commercial SwIAV vaccine was included in a heterologous challenge infection trial. The frequencies of antigen-specific IL-17A and IFNγ secreting CD3 + CD4 low CD8α + CD8β + memory T-helper cells were significantly increased in the lung draining tracheobronchial lymph nodes (TBLN) of intradermal, intramuscular and intranasal inoculated NanoS100-SwIAV vaccine and commercial vaccine administered animals. While the frequencies of antigen-specific, IFNγ secreting CD3 + CD4 low CD8α + CD8β + memory T-helper cells were significantly enhanced in the blood of intranasal and intramuscular vaccinates. These observations suggest that the CD3 + CD4 low CD8α + CD8β + T-helper/memory cells in pigs may have a protective and/or regulatory role/s in immune responses against SwIAV infection. These observations highlight the heterogeneity and plasticity of porcine CD4 + T-helper/memory cells in response to respiratory viral infection in pigs. Comprehensive systems immunology studies are needed to further decipher the cellular lineages and functional role/s of this porcine T helper/memory cell subset.

  PublisherDOI

Recent grants

• NIH Grant R01AR049288

  NIH · $5.9M · 2018

Frequent coauthors

• John P. Sundberg

  36 shared

• Briän Catchpole

  Royal Veterinary College

  23 shared

• Stanley L. Hem

  19 shared

• Anna Sokolovska

  14 shared

• Juan F. Hernandez-Franco

  Purdue University West Lafayette

  13 shared

• Gourapura J. Renukaradhya

  12 shared

• Fangjia Lu

  Purdue University West Lafayette

  12 shared

• Peter J. Felsburg

  University of Pennsylvania

  12 shared

Education

• Ph.D., Pathobiology

  University of Illinois

  1989

• DVM, College of Veterinary Medicine

  University of Utrecht, Netherlands

  1984