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 Department of Health

US Government as Represented by the Secretary of the Army

New York University

Oregon Health & Science University

The United States of America

Virogenetics Corporation

Robert C. Gallo

Enzo Paoletti

Genoveffa Franchini

James Tartaglia

Robert C Gallo

Mikulas Popovic

Phillip D Markham

Marvin S Reitz, Jr

Franco C Lori

Suzanne Gartner

George N Pavlakis

Zdenek Hel

Flossie Wong-Staal

William I Cox

Jay Hooper

Timothy J Cardozo

Rafick-Pierre Sekaly

Luca Schifanella

Shari Gordon

Melvin Doster

Slim Fourati

Namal Malimbada Liyanage

Manuel Becerra-Flores

Giacomo Gorini

Isabela Silva De Castro

Mark Cameron

Massimiliano Bissa

Monica Vaccari

Embodiments of recombinant HIV-1 gp120 proteins that contain a V1 deletion are disclosed. Also provided are gp140, gp145, and gp160 proteins containing the V1 deletion, as well as HIV-1 Env ectodomain trimers containing protomers containing the V1 deletion. Nucleic acid molecules encoding these proteins are also provided. In several embodiments, the disclosed recombinant HIV-1 proteins and/or nucleic acid molecules can be used to generate an immune response to HIV-1 in a subject, for example, to treat or prevent an HIV-1 infection in the subject.

Recombinant gp120 protein with V1-loop deletion

Compositions including a therapeutically effective amount of an HIV immunogen in combination with an agent that stimulates the Ras pathway, wherein the agent is not an aluminum salt, are disclosed. Methods are also disclosed for inducing an immune response to HIV, and/or to inhibit or treat HIV infection, in a subject, using an HIV immunogen and an agent that stimulates the Ras pathway. Methods also are disclosed for determining if an immunogenic composition will induce a protective response, and/or to determine if an immunogenic composition is of use to prevent or treat an HIV infection. The methods including determining if the immunogenic composition increases the level of one or more components of the Ras signaling pathway.

Ras pathways as markers of protection against HIV and methods to improve vaccine efficacy

The invention described here entails a protein vaccine against poxviruses which contains at least two purified recombinant monkeypox virus proteins or peptides. The proteins or peptides are encoded by the open reading frames of the monkeypox ortholog genes M1R, A35R, A29L B6R, and orthologs of these proteins or peptides having 90% identity. The invention also entails a vaccine protocol against poxvirus whereby a vaccine is vaccinated with a first vaccine made up of a nucleic acid vaccine of three or more poxvirus virus genes, and subsequently vaccinated with at least one other booster vaccine made up of two or more poxvirus virus proteins.

Protein vaccines against poxviruses

This invention relates to improved methods of inducing an immune response for the prevention or treatment of HIV-1 infection by using a nucleic acid vaccine in conjunction with a recombinant viral vaccine, e.g., a poxvirus vaccine, to potentiate and broaden the immune response. The present invention further provides a particularly effective vaccine regimen comprising a DNA vaccine used in combination with a poxvirus virus, especially NYVAC or ALVAC.

Methods of potentiating HIV-1-specific CD8+ immune responses involving the concomitant administration of DNA and ALVAC expression vectors

Immunogenicity using a combination of DNA and vaccinia virus vector vaccines

Attenuated recombinant viruses containing DNA encoding an immunodeficiency virus and/or CTL antigen, as well as methods and compositions employing the viruses, expression products therefrom, and antibodies generated from the viruses or expression products, are disclosed and claimed. The recombinant viruses can be NYVAC or ALVAC recombinant viruses. The DNA can code for at least one of: HIV1gag(&plus;pro)(IIIB), gp120(MN)(&plus;transmembrane), nef(BRU)CTL, pol(IIIB)CTL, ELDKWA or LDKW epitopes, preferably HIV1gag(&plus;pro)(IIIB), gp120(MN) (&plus;transmembrane), two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL etpitopes; or two ELDKWA in gp120 V3 or another region or in gp160. The two (2) nef(BRU)CTL and three (3) pol(IIIB)CTL epitopes are preferably CTL1, CTL2, pol1, pol2 and pol3. The recombinant viruses and gene products therefrom and antibodies generated by the viruses and gene products have several preventive, therapeutic and diagnostic uses. DNA from the recombinant viruses are useful as probes or, for generating PCR primers or for immunization. Also disclosed and claimed are HIV immunogens and modified gp160 and gp120.

Immunodeficiency recombinant poxvirus

The present invention relates to the HIV-1 strains MN-ST1 and BA-L which are typical United States HIV-1 isotypes. The present invention relates to DNA segments encoding the envelope protein of MN-ST1 or BA-L, to DNA constructs containing such DNA segments and to host cells transformed with such constructs. The viral isolates and envelope proteins of the present invention are of value for use in vaccines and bioassays for the detection of HIV-1 infection in biological samples, such as blood bank samples.

Molecular clones of HIV-1 viral strains MN-ST1 and BA-L, and uses thereof

The present invention relates to the HIV-1 strains MN-ST1 and BA-L which are typical United States HIV-1 isotypes. The present invention relates to DNA segments encoding the envelope protein of MN-ST 1 or BA-L, to DNA constructs containing such DNA segments and to host cells transformed with such constructs. The viral isolates and envelope proteins of the present invention are of value for use in vaccines and bioassays for the detection of HIV-1 infection in biological samples, such as blood bank samples.

Molecular clones of HIV-1 viral strains MH-ST1 and BA-L, and uses thereof

Molecular clones of HIV-1 viral strains MN-ST1 and BA-L and uses thereof

A complete genomic clone of HIV-2 designated HIV-2.sub.SBL/ISY was cloned from DNA of the neoplastic human cell line HUT78 infected with the HIV-2.sub.SBL6669 viral isolate. The clone was sequenced and the sequence compared with those of known HIV-2 isolates. The invention is advantageous for it provides an animal model for the study of HIV infection in man.

Characterization of replication competent human immunodeficiency type 2

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Washington, DC, United States of America

Genoveffa Franchini