Center for Vaccines and Immunology, Department of Infectious Diseases
CVI Affiliated Faculty, Director of Faculty of Infectious Diseases, GRA Distinguished Investigator, Professor
Expertise
Immunology | Infectious Diseases | Parasitology | Vaccinology | Virology
Biography
Much of modern human disease is inflammation based, from obesity to autoimmune diseases. Inflammation also contributes to damage in stroke, cardiovascular disease and in rejection of organ transplants. Thus there is a need for discovery and development of novel anti-inflammatory agents. Our lab determined that a biologically conserved glycan (LNFPIII) is anti-inflammatory. LNFPIII alternatively activates macrophages and dendritic cells via a non-canonical signaling pathway that drives maturation of anti-inflammatory cells. We have shown that LNFPIII is a potent anti-inflammatory agent in vivo, with broad therapeutic capability. Additionally, administration of LNFPIII to HIV-1 infected cells significantly reduces HIV-1 viral loads. Currently we are employing bioinformatics to determine the activation pathways and immune mediators induced by LNFPIII, in conjunction with knockdown, loss of function studies to discover new anti-inflammatory and anti-retroviral reagents.
Vaccine discovery and development. Schistosomiasis remains a global public health problem, infecting approximately 200 million people. In China, water buffalo account for up to 75% of transmission. Via a field trial in Anhui, we are testing the hypothesis that administration of a schistosome vaccine to buffalo will reduce transmission to humans. In separate trials in Hunan, we are optimizing these vaccines. We are focusing on identifying immune correlates of vaccine efficacy. In addition to causing morbidity and mortality, helminthes are immune suppressive. As helminth infections coincide with those countries with the greatest prevalence of HIV-1, we are examining the negative impact helminth infection may have on vaccines for HIV-1 and other viral diseases.
We are also working to develop a vaccine for HIV-1 utilizing the novel approach of employing viral envelope glycans in a glyco-conjugate vaccine similar to bacterial glyco-conjugate vaccines. Because host machinery lays down viral envelope glycans, these antigens are likely to be stable antigenic targets, and conserved across clades.
Research Interests
- Identification of cell receptors and signaling pathways that drive anti-inflammatory activation of antigen presenting cells
- Development of vaccines and therapeutics for HIV-1 and schistosomiasis
Activities
Much of modern human disease is inflammation based, from obesity to autoimmune diseases. Inflammation also contributes to damage in stroke, cardiovascular disease and in rejection of organ transplants. Thus there is a need for discovery and development of novel anti-inflammatory agents. Our lab determined that a biologically conserved glycan (LNFPIII) is anti-inflammatory. LNFPIII alternatively activates macrophages and dendritic cells via a non-canonical signaling pathway that drives maturation of anti-inflammatory cells. We have shown that LNFPIII is a potent anti-inflammatory agent in vivo, with broad therapeutic capability. Additionally, administration of LNFPIII to HIV-1 infected cells significantly reduces HIV-1 viral loads. Currently we are employing bioinformatics to determine the activation pathways and immune mediators induced by LNFPIII, in conjunction with knockdown, loss of function studies to discover new anti-inflammatory and anti-retroviral reagents.
Vaccine discovery and development. Schistosomiasis remains a global public health problem, infecting approximately 200 million people. In China, water buffalo account for up to 75% of transmission. Via a field trial in Anhui, we are testing the hypothesis that administration of a schistosome vaccine to buffalo will reduce transmission to humans. In separate trials in Hunan, we are optimizing these vaccines. We are focusing on identifying immune correlates of vaccine efficacy. In addition to causing morbidity and mortality, helminthes are immune suppressive. As helminth infections coincide with those countries with the greatest prevalence of HIV-1, we are examining the negative impact helminth infection may have on vaccines for HIV-1 and other viral diseases.
We are also working to develop a vaccine for HIV-1 utilizing the novel approach of employing viral envelope glycans in a glyco-conjugate vaccine similar to bacterial glyco-conjugate vaccines. Because host machinery lays down viral envelope glycans, these antigens are likely to be stable antigenic targets, and conserved across clades.
Selected Publications
- Shollenberger LM, Bui C, Paterson Y, Allen K, Harn D. Successful vaccination of immune suppressed recipients using Listeria vector HIV-1 vaccines in helminth infected mice. Vaccine. 2013 Mar 5.
- Grenfell R, Harn DA, Tundup S, Da’dara A, Siqueira L, Coelho PM. New Approaches with Different Types of Circulating Cathodic Antigen for the Diagnosis of Patients with Low Schistosoma mansoni Load. PLoS Negl Trop Dis. 2013 Feb;7(2):e2054.
- Bhargava P, Li C, Stanya KJ, Jacobi D, Dai L, Liu S, Gangl MR, Harn DA, Lee CH. Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways. Nat Med. 2012 Nov;18(11):1665-72
- Tundup S, Srivastava L, Harn DA Jr. Polarization of host immune responses by helminth-expressed glycans. Ann N Y Acad Sci. 2012 Apr;1253:E1-E13.
- Marrache S, Choi JH, Tundup S, Zaver D, Harn DA, Dhar S. Immune stimulating photoactive hybrid nanoparticles for metastatic breast cancer. Integr Biol (Camb). 2013 Jan;5(1):215-23.
- Zhu B, Trikudanathan S, Zozulya AL, Sandoval-Garcia C, Kennedy JK, Atochina O, Norberg T, Castagner B, Seeberger P, Fabry Z, Harn D, Khoury SJ, Guleria I. Immune modulation by Lacto-N-fucopentaose III in experimental autoimmune encephalomyelitis. Clin Immunol. 2012 Mar;142(3):351-61.
- Dutta P, Hullett DA, Roenneburg DA, Torrealba JR, Sollinger HW, Harn DA, Burlingham WJ. Lacto-N-fucopentaose III, a pentasaccharide, prolongs heart transplant survival. Transplantation. 2010 Nov 27;90(10):1071-8.
- Da’dara AA, Harn DA. Elimination of helminth infection restores HIV-1C vaccine-specific T cell responses independent of helminth-induced IL-10. Vaccine. 2010 Feb 3;28(5):1310-7.
- Wang Y, Da’Dara AA, Thomas PG, Harn DA. Dendritic cells activated by an anti-inflammatory agent induce CD4(+) T helper type 2 responses without impairing CD8(+) memory and effector cytotoxic T-lymphocyte responses. Immunology. 2010 Mar;129(3):406-17.
- Dai Y, Zhu Y, Harn DA, Wang X, Tang J, Zhao S, Lu F, Guan X. DNA vaccination by electroporation and boosting with recombinant proteins enhances the efficacy of DNA vaccines for Schistosomiasis japonica. Clin Vaccine Immunol. 2009 Dec;16(12):1796-803.
