The United States of America As Represented by the Department of Health

Biological Mimetics, Inc.

The United States of America, As Represented by the Secretary, Department of Health and Human Services

The United States of America As Represented by the Secretary of

New York University

American Biosciences, Inc.

Peter L Nara

Jay A Berzofsky

Gregory J Tobin

Mutsunori Shirai

Jeffrey D Ahlers

C David Pendleton

George Lin

Jaap Goudsmit

Hsiang-fu Kung

Robert R Garrity

Paul L Huang

Sylvia Lee-Huang

Stephen Oroszlan

Peter Huang

Philip L Huang

Hao-Chia Chen

Henry I Huang

Wen-Po Tsai

C David Pendelton

Methods for providing novel compositions useful as influenza immunogens are provided. The compositions enable a host response to immunogen sites normally not recognized by a host. The novel immunogens can be used as vaccines or to develop antibodies.

Immunogenic influenza composition

Novel compositions useful as influenza immunogens are provided. The compositions enable a host response to immunogen sites normally not recognized by a host.

Novel compositions useful as human rhinovirus immunogens are provided. The compositions enable a host response to sites normally not recognized by a host.

Immunogenic human rhinovirus (HRV) compositions

Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the Dclass I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

Peptides which elicit a high neutralizing antibody titer, cytotoxic T lymphocyte response and T helper cell response in a broad range of MHC type recipients

Peptide constructs comprised of multideterminant T helper peptides from the envelope glycoprotein of HIV previously identified to induce proliferative responses in four different haplotypes of mice and IL-2 responses in 52-73% of HIV positive, flu positive patients (cluster peptides), were co-linearly synthesized with the peptide 18 of the V3 loop of HIV-1 gp 160, corresponding to the principal neutralizing determinant of HIV-IIIB and also shown to contain a dominant CTL epitope. Cognate help for peptide 18 antibody was elicited following a single immunization in all strains of mice which had previously responded to a T cell epitope encompassed by the peptides. In two strains of mice, the level of neutralizing antibody achieved was comparable to levels adequate for protection from homologous viral challenge in chimpanzees. After a single boost, much higher antibody titers for 90% neutralization in the range of 1:1000 to 1:16,000 were achieved. Spleen cells from mice of three distinct MHC haplotypes sharing the D,class I MHC molecule but with different class II molecules, immunized with the compound peptides, exhibited enhanced gp160-specific CTL activity.

Multideterminant peptides that elicit helper T-lymphocyte cytotoxic T-lymphocyte and neutralizing antibody responses against HIV-1

The invention is directed to peptides of the HIV-1 envelope protein presenting multiple immune determinants. The peptide elicits both humoral and cell-mediated immune responses in mice having a variety of MHC types. In other embodiments, the invention is directed to immunogens composed of the peptides and methods for immunization employing them.

Multideterminant peptides that elicit helper T-lymphocyte, cytotoxic T lymphocyte and neutralizing antibody responses against HIV-1

This invention is directed toward a multideterminant human immunodeficiency virus type 1 (HIV-1) peptide which comprises a covalently linked T-helper (Th) lymphocyte epitope, cytotoxic T-lymphocyte (CTL) epitope, and an epitope capable of eliciting a neutralizing antibody response (AbN), wherein said peptide has the following amino acid sequence: KQIINMWQEVGKAMYAPPISGQIRRIHIGPGRAFYTTKN. This peptide has the further characteristic of evoking all three of these immune responses in hosts having a broad range of major histocompatibility complex (MHC) types. This peptide is useful as an immunogen to generate broad immune responses in a host, to assess immune responses in virally infected hosts, and as a diagnostic reagent to detect viral infection.

Multideterminant peptides eliciting helper T-lymphocyte, cytotoxic

The present invention provides a vaccine that can be administered to a mammal to cause immunoprotection in the mammal against a pathogenic organism that has an immunodominant epitope. The vaccine includes a modified form of the antigen in which the immunodominant epitope is located. In this modified form, the immunodominant epitope is immunodampened by any of a number of techniques. Examples of immunodampening techniques include addition of N-linked glycosylation sites, change of the net charge on the epitope, and substitution with a tolerated sequence. The vaccine also includes a pharmacologically acceptable carrier.

Dampening of an immunodominant epitope of an antigen for use in plant,

Methods are disclosed for inhibiting the infectivity of HIV-1 in human cells. The methods comprise contacting human cells infected with HIV-1, with certain quinolinyl and acridinyl derivatives, including amodiaquin, chloroquine, hydroxychloroquine, primoquine, quinacrine and compounds having the formula: ##STR1## wherein R.sup.1 and R.sup.2 are each hydrogen, or join to form a cyclic structure of the formula: ##STR2## and R.sup.3 and R.sup.4, same or different, are hydrogen, C.sub.1 -C.sub.8 lower alkyl or hydroxy substituted C.sub.1 -C.sub.8 lower alkyl, and the pharmaceutically acceptable salts thereof.

Inhibition of human immunodeficiency virus-1 infectivity in human cells

The present invention provides a composition that can be administered to a mammal to cause immunoprotection in the mammal against a pathogenic organism that has an immunodominant epitope. The composition includes a modified form of the antigen in which the immunodominant epitope is located. In this modified form, the immunodominant epitope is immunodampened by any of a number of techniques. Examples of immunodampening techniques include addition of N-linked glycosylation sites, change of the net charge on the epitope, and substitution with a tolerated sequence. The composition also includes a pharmacologically acceptable carrier.

A protein, in particular MAP 30, obtainable from both the fruit and seeds of Momordica charantia or produced by recombinant means useful for treating tumors and HIV infections is disclosed. In treating HIV infections, the protein is administered alone or in conjunction with conventional AIDS therapies. Also provided are processes for purifying the protein, DNA sequences encoding the protein, and recombinant DNA methods for expressing the protein.

Growing community of inventors

Frederick, MD, United States of America

Peter L Nara