University of Massachusetts

New York University

St. Jude Children's Research Hospital

Molsoft LLC

Advanced Bioscience Laboratories, Inc.

Shan Lu

Shixia Wang

Susan Zolla-Pazner

Maxim Totrov

Harriet L Robinson

Robert G Webster

Timothy J Cardozo

Ellen F Fynan

Xiang-peng Kong

Abraham Pinter

Ranajit Pal

Ruben Abagyan

John E Herrmann

Miroslaw K Gorny

Stephen Whitney

Vaniambadi Kalyanaraman

Balachandran Nair

Phillip Markham

Pavlo Sakhatskyy

Tim Keen

Stephen Charles Whitney

Balachandran C Nair

V S Kalyanaraman

Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV are disclosed. The compositions and methods described herein are for the use of a nucleic acid composition that encodes one or more different HIV envelope glycoproteins. The synthetic, codon-optimized DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV polypeptide compositions for inducing an immune response against HIV are also disclosed. Methods for using the polypeptide compositions before, at the same time as, and/or after administration of the DNA compositions are provided.

Compositions and methods to treat aids

Compositions and methods to treat AIDS

The present invention is directed to a recombinant immunogenic polypeptide. The polypeptide includes a loop peptide inserted into an immunogenic scaffold protein. The loop polypeptide has an amino acid sequence which presents the 3074 mAb- or the 2219/2557 mAb-targeted epitope of the HIV gp120 protein and not other known epitopes of the HIV gp120 protein. When used as an immunogen, the polypeptide induces an antibody response which neutralizes heterologous HIV-1 viruses in a pattern similar to that observed for the 3074 mAb- or the 2219/2557 mAb-targeted epitope, respectively. Pharmaceutical compositions containing the immunogenic polypeptide as well as methods of making and using it are also disclosed.

Immunogenic polypeptides comprising a modified loop peptide presenting the HIV-1 GP120 3074 mAb epitope and scaffold proteins containing said peptide

Insertion of HIV-1 V3 loop peptides from the viral glycoprotein gp120 into selected, immunogenic scaffold proteins results in a recombinant polypeptide that is a potent V3 immunogen. V3 immunogens include natural and consensus V3 sequences and cyclic and reverse peptides. Preferred scaffold proteins are Cholera Toxin subunit B and homologues thereof including closely relatedenterotoxins. Such immunogenic polypeptides induce broadly reactive anti-gp120 antibodies specific for V3 epitopes that can neutralize heterologous HIV-1 subtypes and strains. These polypeptide, methods for preparing them, and methods for inducing anti-gp120 (V3-specific) antibody) responses using them are disclosed.

Immunogen comprising the HIV GP120 V3 loop in a conformation that induces broadly neutralizing antibodies

Polyvalent, primary isolate nucleic acid compositions for inducing an immune response against HIV is disclosed. The composition and methods described herein are for the use of a DNA composition that encodes one or more different HIV envelope glycoproteins. The DNA composition can encode an HIV Gag protein. The DNAs encoding one or more HIV proteins are a combination of different nucleic acids, such as DNA plasmids, generated from primary isolate DNA of different HIV major group genetic clades and/or different proteins. HIV protein compositions for inducing an immune response against HIV are disclosed. Methods fro using the protein compositions as boosts following administration of the DNA compositions are provided.

Polyvalent, primary HIV-1 glycoprotein DNA vaccines and vaccination methods

This invention relates to a method of immunizing a vertebrate, comprising introducing into the vertebrate a DNA transcription unit which comprises DNA encoding a desired antigen or antigens. The uptake of the DNA transcription unit by a host vertebrate results in the expression of the desired antigen or antigens, thereby eliciting humoral or cell-mediated immune responses or both humoral and cell-mediated responses. The elicited humoral and cell-mediated immune response can provide protection against infection by pathogenic agents, provide an anti-tumor response, or provide contraception. The host can be any vertebrate, avian or mammal, including humans.

Immunization by inoculation of DNA transcription unit

A novel immunogenic HIV-1 Env, particularly gp120, DNA construct is disclosed in which either the V1/V2 loop and the V4 loop, or all three variable loops, including V3, are replaced with a V3 sequence each of which is from a different viral isolate. Preferably, each replacement V3 loop is a consensus sequence of V3 of a different clade. Such constructs are useful as immunogens as each presents three independent V3 epitopes, so that the immunized subject generates a more broadly reactive neutralizing antibody response than with conventional gp120 or V3 DNA or polypeptide immunogens. Also disclosed are methods of using the DNA construct to immunize a mammal, preferably a human, particularly in a priming regiment in which the DNA immunogen is followed by administration of a V3 fusion protein boosting immunogen.

Recombinant HIV-1 gp120 immunogen with three different V3 loops from viruses of different clades

Methods and compositions for inducing immune responses against poxviruses are disclosed. The compositions include nucleic acids that encode modified vaccinia and variola antigens. Compositions that include recombinant vaccinia and variola polypeptides are also disclosed.

Poxvirus methods and compositions

Codon-optimized nucleic acids encoding influenza polypeptides and uses of the nucleic acids and polypeptides for inducing immune responses are provided herein.

Influenza nucleic acids, polypeptides, and uses thereof

A method of producing an effective immune response in an animal against a first rotavirus, by (1) identifying an animal susceptible to or having a first rotavirus infection; and (2) administering to the animal an isolated VP6 polypeptide of a second rotavirus sufficient to produce an effective immune response against the first rotavirus, the second rotavirus capable of infecting a different species than the first rotavirus.

Cross-protective rotavirus vaccine

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Franklin, MA, United States of America

Shan Lu