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

Genvec, Inc.

Genvex, Inc.

Crucell Holland B.v.

Bimal Chakrabarti

Gary J Nabel

Zhi-yong Yang

Yue Huang

Wing-Pui Kong

Zengguang Wang, Legal Representative

Maria Grazia Pau

C Richter King

Jason G D Gall

Jaap Goudsmit

Nancy J Sullivan

Ling Xu

Lan Wu

Lan VRC/NIAID/NIH Wu

The invention is related to a nucleic acid molecule comprising a polynucleotide encoding a modified filovirus glycoprotein (GP) having at least one amino acid change located in a relatively conserved region of said GP that decreases in vitro cytotoxicity and retains immunogenicity when compared to in vitro cytotoxicity and immunogenicity of a wild type filovirus GP, and related modified filovirus GPs, plasmid DNAs, recombinant viruses, adenoviruses, pharmaceutical compositions, vaccine compositions, antibodies that are specifically reactive with the modified filovirus GPs, and related methods of making and using the same.

Nucleic acids encoding modified Ebola virus glycoproteins with diminished cytotoxicity while retaining native antigenic structures

The present disclosure provides compositions for eliciting an immune response, including a prophylactic immune response, against human immunodeficiency virus. The composition includes nucleic acid constructs encoding HIV antigenic polypeptides of multiple clades or strains. Methods for eliciting an immune response by administering the composition to a subject are also provided.

Method for inducing a multiclade immune response against HIV utilizing a multigene and multiclade immunogen

The invention provides a composition comprising four adenoviral vectors, each comprising a nucleic acid sequence encoding a clade A HIV Env protein, a clade B HIV Env protein, a clade C HIV Env protein, and a clade B HIV Gag-Pol fusion protein, respectively. The invention also provides a method of inducing an immune response against HIV-1 in an animal comprising administering the composition to the animal.

HIV vaccines based on adenoviral vectors encoding Env from multiple clades of HIV

Recombinant expression vectors comprising a human codon-optimized marburg virus (MARV) angola glycoprotein gene insert and method of immunization employing said vector

The invention provides a composition comprising a pharmaceutically acceptable carrier and six plasmids, each of which encodes an HIV Env, Gag, Pol, or Nef protein. The invention also provides a method of inducing an immune response in an animal using the composition.

HIV vaccines based on Env of multiple clades of HIV

In one embodiment, the invention provides a multiclade HIV plasmid DNA or viral vector vaccine including components from different clades of Env (optionally Env chimeras) and Gag-Pol-(optionally)Nef from a single clade. The vaccine of the invention may further include V1, V2, V3, or V4 deletions or combinations thereof. In another embodiment, the invention provides multiclade HIV envelope immunogens.

Modified HIV Env, Gag, Pol, or Nef DNA with improved ability to elicit antibody and CTL responses to HIV antigens have been identified as prototype immunogens for the treatment and prevention of HIV infections. Modifications to Env glycoprotein include deletions in the cleavage site, fusogenic domain, and spacing of heptad repeats 1 and 2 and different COOH-terminal deletions. Other modifications entail expression of Gag-Pol and Gag-Pol-Nef as fusion proteins.

Modifications of HIV, ENV, GAG, and POL enhance immunogenicity for genetic immunization

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Gaithersburg, MD, United States of America

Bimal Chakrabarti