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.
- Da’dara AA, Li YS, Xiong T, Zhou J, Williams GM, McManus DP, Feng Z, Yu XL, Gray DJ, Harn DA. DNA-based vaccines protect against zoonotic schistosomiasis in water buffalo. Vaccine. 2008 Jul 4;26(29-30):3617-25. Epub 2008 May 19.
- Atochina O, Da’dara AA, Walker M, Harn DA. The immunomodulatory glycan LNFPIII initiates alternative activation of murine macrophages in vivo. Immunology. 2008 Mar 28. [Epub ahead of print]
- Reis EA, Mauadi Carmo TA, Athanazio R, Reis MG, Harn Jr DA. Schistosoma mansoni Triose Phosphate Isomerase Peptide MAP4 is Able to Trigger Na•ve Donor Immune Response Towards a Type-1 Cytokine Profile. Scand J Immunol. 2008 Jun 18. [Epub ahead of print]
- Da’Dara AA, Lautsch N, Dudek T, Novitsky V, Lee TH, Essex M, Harn DA. Helminth infection suppresses T-cell immune response to HIV-DNA-based vaccine in mice. Vaccine. 2006 Jun 12;24(24):5211-9. Epub 2006 Apr 18.
- Atochina O, Harn D. Prevention of psoriasis-like lesions development in fsn/fsn mice by helminth glycans. Exp Dermatol. 2006 Jun;15(6):461-8.
- Pashov AD, Plaxco J, Kaveri SV, Monzavi-Karbassi B, Harn D, Kieber-Emmons T. Multiple antigenic mimotopes of HIV carbohydrate antigens: relating structure and antigenicity. J Biol Chem. 2006 Oct 6;281(40):29675-83.
- Thomas PG, Carter MR, Da’dara AA, DeSimone TM, Harn DA. A helminth glycan induces APC maturation via alternative NF-kappa B activation independent of I kappa B alpha degradation. J Immunol. 2005 Aug 15;175(4):2082-90.