The long-term objective is the development of fully synthetic immunogens, suitable for elicitation of long-term protective immunity in humans against human T-lymphotrophic virus type III (HTLV-III) [=lymphadenopathy-associated virus (LAV) or AIDS-associated retrovirus (ARV); abbreviated in the following text as HTLV-3], and resulting in prevention of the acquired immune deficiency syndrome (AIDS), and probably of other diseases associated with HTLV-3 infections, for example Kaposi sarcoma, lymphomas, etc. Peptides corresponding to segments of the amino acid sequence deduced from the nucleotide sequence of the HTLV-3 (clone BH10) envelope (env) protein will be synthesized and used to immunize experimental animals. The resulting antisera will be tested for antibodies (a) reacting with the homologous peptides, (b) reacting with HTLV-3 env proteins and (c) neutralizing the infectivity of the HTLV-3-BH10. The reactivity of antibodies from human sera (positive for anti-HTLV-3 and containing antibodies neutralizing the infectivity of HTLV-3 [VN-Ab] with the synthetic peptides will be tested. The ability of synthetic peptides to react with VN-Ab will be assessed in immunochromatography experiments. Peptides reacting with human VN-Ab and eliciting VN-Ab in experimental animals will be selected for more detailed studies. The sequence variability between HTLV-3 env protein regions, corresponding to distinct HTLV-3 isolates, demarcated by the selected peptide(s) will be assessed from available sequencing data. If warranted by sequence variability, additional peptides [differing in sequence but not in position along the env protein] will be synthesized. The immunological cross-reactivity between the peptides and their ability to induce VN-Ab against distinct HTLV-3 isolates will be determined. The possibility of shifts in the localization of VN epitopes along the env sequences of distinct viral isolates will also be considered. The proposed experiments are expected to result in identification of a few related synthetic analogs, which can be synthesized simultaneously and form the basis of a """"""""multivalent"""""""" vaccine eliciting broad protection against HTLV-3 """"""""subtypes"""""""".

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA043315-01
Application #
3185491
Study Section
(SRC)
Project Start
1986-09-01
Project End
1989-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
New York Blood Center
Department
Type
DUNS #
City
New York
State
NY
Country
United States
Zip Code
10065
Seppala, M; Jiang, S; Strick, N et al. (1997) Glycodelins GdA and GdS modified by 3-hydroxyphthalic anhydride inhibit gp120-CD4 binding and HIV-1 infection in vitro. Lab Invest 77:127-30
Neurath, A R; Li, Y Y; Strick, N et al. (1996) A herpesvirus inhibitor from bovine whey. Lancet 347:1703-4
Neurath, A R; Jiang, S; Strick, N et al. (1996) Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV. Nat Med 2:230-4
Jiang, S; Lin, K; Strick, N et al. (1996) Chemically modified bovine beta-lactoglobulin blocks uptake of HIV-1 by colon- and cervix-derived epithelial cell lines. J Acquir Immune Defic Syndr Hum Retrovirol 13:461-2
Neurath, A R; Debnath, A K; Strick, N et al. (1995) Blocking of CD4 cell receptors for the human immunodeficiency virus type 1 (HIV-1) by chemically modified bovine milk proteins: potential for AIDS prophylaxis. J Mol Recognit 8:304-16
Neurath, A R; Lin, K; Strick, N et al. (1995) Two partially overlapping antiviral peptides from the external portion of HIV type 1 glycoprotein 41, adjoining the transmembrane region, affect the glycoprotein 41 fusion domain. AIDS Res Hum Retroviruses 11:189-90
Neurath, A R; Strick, N; Debnath, A K (1995) Structural requirements for and consequences of an antiviral porphyrin binding to the V3 loop of the human immunodeficiency virus (HIV-1) envelope glycoprotein gp120. J Mol Recognit 8:345-57
Neurath, A R; Strick, N; Lin, K et al. (1995) Multifaceted consequences of anti-gp41 monoclonal antibody 2F5 binding to HIV type 1 virions. AIDS Res Hum Retroviruses 11:687-96
Debnath, A K; Jiang, S; Strick, N et al. (1994) Three-dimensional structure-activity analysis of a series of porphyrin derivatives with anti-HIV-1 activity targeted to the V3 loop of the gp120 envelope glycoprotein of the human immunodeficiency virus type 1. J Med Chem 37:1099-108
Jiang, S; Lin, K; Strick, N et al. (1993) Inhibition of HIV-1 infection by a fusion domain binding peptide from the HIV-1 envelope glycoprotein GP41. Biochem Biophys Res Commun 195:533-8

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