Abstract

The overall goal of this project is to identify leishmanial antigens that have diagnostic and immunoprophylactic potential and to clone the corresponding antigen genes to enable production of large quantities of the antigens. Antigens with diagnostic potential will be identified initially using immunoprecipitation and immunoblot assays employing sera from humans with current or past infections. The diagnostic utility of these antigens derived from both the parasite or cloned parasite genes will be confirmed using serological (ELISA) assays. Protective antigens will be initially identified using a series of in vitro assays employing T lymphocytes, including human and mouse T cell lines and clones. Confirmatory assays of the ability of these antigens to protect against infection will be tested in animal systems. Recombinant DNA libraries will be prepared from mRNA (cDNA) and genomic DNA using standard techniques. The cloned genes of interest will be identified using immunoscreening and screening with synthetic oligonucleotides. The identity of the isolated cloned genes as the antigens of interest will be confirmed and the cloned genes will be modified if needed to optimize antigen production. The antigen products of the cloned genes will be tested for their utility as diagnostic and immunoprophylactic reagents.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025038-02
Application #
3138363
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1987-08-01
Project End
1990-07-31
Budget Start
1988-08-01
Budget End
1989-07-31
Support Year
2
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Seattle Biomedical Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98109

  Publications

Reed, Steven G; Carter, Darrick; Casper, Corey et al. (2018) Correlates of GLA family adjuvants' activities. Semin Immunol 39:22-29
Duthie, Malcolm S; Van Hoeven, Neal; MacMillen, Zachary et al. (2018) Heterologous Immunization With Defined RNA and Subunit Vaccines Enhances T Cell Responses That Protect Against Leishmania donovani. Front Immunol 9:2420
Duthie, Malcolm S; Lison, Aurore; Courtenay, Orin (2018) Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis. Trends Parasitol 34:881-890
Duthie, Malcolm S; Reed, Steven G (2017) Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis. Clin Vaccine Immunol 24:
Sato, Camila Massae; Sanchez, Maria Carmen Arroyo; Celeste, Beatriz Julieta et al. (2017) Use of Recombinant Antigens for Sensitive Serodiagnosis of American Tegumentary Leishmaniasis Caused by Different Leishmania Species. J Clin Microbiol 55:495-503
Reed, S G; Coler, R N; Mondal, D et al. (2016) Leishmania vaccine development: exploiting the host-vector-parasite interface. Expert Rev Vaccines 15:81-90
Desbien, Anthony L; Dubois Cauwelaert, Natasha; Reed, Steven J et al. (2016) IL-18 and Subcapsular Lymph Node Macrophages are Essential for Enhanced B Cell Responses with TLR4 Agonist Adjuvants. J Immunol 197:4351-4359
Reed, Steven G; Hsu, Fan-Chi; Carter, Darrick et al. (2016) The science of vaccine adjuvants: advances in TLR4 ligand adjuvants. Curr Opin Immunol 41:85-90
Duthie, Malcolm S; Favila, Michelle; Hofmeyer, Kimberley A et al. (2016) Strategic evaluation of vaccine candidate antigens for the prevention of Visceral Leishmaniasis. Vaccine 34:2779-86
Hofmeyer, Kimberly A; Duthie, Malcolm S; Laurance, John D et al. (2016) Optimizing Immunization Strategies for the Induction of Antigen-Specific CD4 and CD8 T Cell Responses for Protection against Intracellular Parasites. Clin Vaccine Immunol 23:785-94

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