Genes and Gene Products as Immuno-Adjuvants

Holland, S M.

Abstract

This project is directed at understanding, characterizing, and evaluating a novel form of gene product delivery for immunization and treatment: direct DNA injection. Cytokines will be administered intramuscularly to mice in the form of either a cDNA expression vector or preformed protein simultaneously or in sequence with cDNAs for specific antigens from chlamydia in order to elicit a strong immune response. Animals will be followed by evaluation of cytokine response in the circulation, local response to the injected materials at the site of administration, and development and type of immunity. To these ends we have obtained and/or engineered into expressible forms the cDNAs for murine TNF-alpha, murine IL-2, murine IL-4, and murine IL-6. In order to develop the source for the chlamydial antigens needed for these studies, we have generated DNA libraries in a bacterial plasmid system from both Chlamydia trachomatis and Chlamydia pneumoniae. From these libraries we have cloned the genes for the chlamydial major outer membrane proteins and the chlamydial 57kd heat shock protein. These genes have been transferred into bacterial and eukaryotic expression systems.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000647-02
• Application #: 3768879
• Support Year: 2
• Fiscal Year: 1993

Institution

• Name: National Institute of Allergy and Infectious Diseases
• Country: United States

Publications

Xie, Yingda L; Rosen, Lindsey B; Sereti, Irini et al. (2016) Severe Paradoxical Reaction During Treatment of Disseminated Tuberculosis in a Patient With Neutralizing Anti-IFN? Autoantibodies. Clin Infect Dis 62:770-773

Spinner, Michael A; Ker, Jennifer P; Stoudenmire, Charles J et al. (2016) GATA2 deficiency underlying severe blastomycosis and fatal herpes simplex virus-associated hemophagocytic lymphohistiocytosis. J Allergy Clin Immunol 137:638-40

Uzel, Gulbu; Sampaio, Elizabeth P; Lawrence, Monica G et al. (2013) Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation-polyendocrinopathy-enteropathy-X-linked-like syndrome. J Allergy Clin Immunol 131:1611-23

Palmore, Tara N; Shea, Yvonne R; Conville, Patricia S et al. (2009) ""Mycobacterium tilburgii,"" a newly described, uncultivated opportunistic pathogen. J Clin Microbiol 47:1585-7

Zelazny, Adrian M; Root, Jeremy M; Shea, Yvonne R et al. (2009) Cohort study of molecular identification and typing of Mycobacterium abscessus, Mycobacterium massiliense, and Mycobacterium bolletii. J Clin Microbiol 47:1985-95

Elloumi, Houda Zghal; Holland, Steven M (2008) Complex regulation of human cathelicidin gene expression: novel splice variants and 5'UTR negative regulatory element. Mol Immunol 45:204-17

Sampaio, Elizabeth P; Elloumi, Houda Z; Zelazny, Adrian et al. (2008) Mycobacterium abscessus and M. avium trigger Toll-like receptor 2 and distinct cytokine response in human cells. Am J Respir Cell Mol Biol 39:431-9

Uzel, Gulbu; Tng, Emilia; Rosenzweig, Sergio D et al. (2008) Reversion mutations in patients with leukocyte adhesion deficiency type-1 (LAD-1). Blood 111:209-18

Freeman, Alexandra F; Holland, Steven M (2008) The hyper-IgE syndromes. Immunol Allergy Clin North Am 28:277-91, viii

Holland, Steven M (2007) Interferon gamma, IL-12, IL-12R and STAT-1 immunodeficiency diseases: disorders of the interface of innate and adaptive immunity. Immunol Res 38:342-6