HLA and Vaccines (BAA)

Sette, Alessandro D.

Abstract

The overall objective of this contract is to identify and modify the structure of peptides to increase their potency and broaden their specificity with regard to the MHC restriction elements that can recognize them and present them to the human immune system. The result of these efforts should pave the way for testing the feasibility of peptide-based vaccines to prevent and/or treat important human infectious diseases. The specific diseases targeted with these studies are malaria caused by P. falciparum, human immunodeficiency virus (HIV) infection, and hepatitis B virus (HBV) infection.
Specific aims : 1) To identify and modify human class I restricted apitopes such that a single peptide will be recognized and be immunogenic when presented by multiple HLA-A, B or C alleles; 2) To identify and modify human class II restricted apitopes such that a single peptide will be recognized and be immunogenic when presented by multiple HLA-DR alleles: 3) To combine the MHC class II epitopes defined under Specific Aim (2) with cytotoxic T lymphocytes (CTL) and B cell epitopes to produce highly immunogenic, broadly crossreactive CTL responses and antibody responses.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research and Development Contracts (N01)
• Project #: N01AI045241-010
• Application #: 2902082
• Project Start: 1994-09-30
• Project End: 1999-09-29
• Budget Start: 1998-11-05
• Budget End: 1999-09-29
• Fiscal Year: 1999

Institution

• Name: Cytel Corporation
• City: San Diego
• State: CA
• Country: United States
• Zip Code: 92121

Publications

Alexander, Jeff; Oseroff, Carla; Sidney, John et al. (2003) Derivation of HLA-B*0702 transgenic mice: functional CTL repertoire and recognition of human B*0702-restricted CTL epitopes. Hum Immunol 64:211-23

Sette, Alessandro; Sidney, John; Livingston, Brian D et al. (2003) Class I molecules with similar peptide-binding specificities are the result of both common ancestry and convergent evolution. Immunogenetics 54:830-41

Sidney, J; Southwood, S; Mann, D L et al. (2001) Majority of peptides binding HLA-A*0201 with high affinity crossreact with other A2-supertype molecules. Hum Immunol 62:1200-16

Doolan, D L; Southwood, S; Chesnut, R et al. (2000) HLA-DR-promiscuous T cell epitopes from Plasmodium falciparum pre-erythrocytic-stage antigens restricted by multiple HLA class II alleles. J Immunol 165:1123-37

Gianfrani, C; Oseroff, C; Sidney, J et al. (2000) Human memory CTL response specific for influenza A virus is broad and multispecific. Hum Immunol 61:438-52

Rongcun, Y; Salazar-Onfray, F; Charo, J et al. (1999) Identification of new HER2/neu-derived peptide epitopes that can elicit specific CTL against autologous and allogeneic carcinomas and melanomas. J Immunol 163:1037-44

Franke, E D; Hoffman, S L; Sacci Jr, J B et al. (1999) Pan DR binding sequence provides T-cell help for induction of protective antibodies against Plasmodium yoelii sporozoites. Vaccine 17:1201-5

Chang, K M; Gruener, N H; Southwood, S et al. (1999) Identification of HLA-A3 and -B7-restricted CTL response to hepatitis C virus in patients with acute and chronic hepatitis C. J Immunol 162:1156-64

Ishioka, G Y; Fikes, J; Hermanson, G et al. (1999) Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. J Immunol 162:3915-25

Kawashima, I; Tsai, V; Southwood, S et al. (1999) Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res 59:431-5