University of Washington

The Scripps Research Institute

International Aids Vaccine Initiative

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

Massachusetts Institute of Technology

William Ray Schief

Gary J Nabel

Peter D Kwong

John R Mascola

Tongqing Zhou

Zhi-yong Yang

Mark Connors

Richard Wyatt

Xueling Wu

Mario Roederer

Yuxing Li

Sergey V Menis

Carl-Magnus Hogerkorp

Joseph Graham Jardine

Neil P King

Po-Ssu Huang

Bruno E Correia

Daniel Kulp

Darrell J Irvine

Tyson Moyer

Jon M Steichen

Sebastian Raemisch

Ron Jacak

Dan Kulp

Xiaozhen Hu

The present invention relates to engineered outer domain (eOD) immunogens of HIV gp120 and mutants thereof and methods of making and using the same. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity. The mutant eODs bind to neutralizing antibody precursors. The mutant eODs can activate germline precursors on the pathway to eliciting a broadly neutralizing antibody (bnAb) response. The invention also relates to immunized knock-in mice expressing germline-reverted heavy chains. Induced antibodies showed characteristics of bnAbs and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate precursors. The invention also relates to rational epitope design that can prime rare B cell precursors for affinity maturation to desired targets.

Engineered outer domain (eOD) of HIV GP120, mutants and use thereof

The present disclosure relates to compositions and methods for coupling an antigen to an adjuvant, immunogenic compositions and vaccines. The methods of the invention can be used to increase an immune response, or to treat cancer or an infectious disease.

Antigen-adjuvant coupling reagents and methods of use

The invention relates to PGT121-germline-targeting designs, trimer stabilization designs, combinations of those two, trimers designed with modified surfaces helpful for immunization regimens, other trimer modifications and on development of trimer nanoparticles and methods of making and using the same.

Immunogenic trimers

The invention relates to an engineered outer domain (eOD) of HIV gp120 and mutants thereof and methods of making and using the same. The mutant eODs may be advantageous for the elicitation of CD4-binding site (CD4bs)-directed broadly-neutralizing antibodies (bnAbs) and/or improve binding to mature VRC01 and/or improve binding to germline VRC01 and the germlines of other VH1-2 derived broadly-neutralizing antibodies. The mutant eODs may also include glycan-masking mutations on eOD. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity as well as the design of cocktails of different eODs that represent the full diversity of HIV sequences within the VRC01 epitope and surroundings.

Engineered outer domain (EOD) of HIV GP120 and mutants thereof

Engineered outer domain (eOD) of HIV gp120 and mutants thereof

Monoclonal neutralizing antibodies are disclosed that specifically bind to the CD4 binding site of HIV-1 gp120. Monoclonal neutralizing antibodies also are disclosed that specifically bind to HIV-1 gp41. The identification of these antibodies, and the use of these antibodies are also disclosed. Methods are also provided for enhancing the binding and neutralizing activity of any antibody using epitope scaffold probes.

Neutralizing antibodies to HIV-1 and their use

The present invention provides polypeptides and compositions thereof for treating or limiting respiratory syncytial virus infection, and computational methods for designing such polypeptides.

Polypeptides and their use in treating and limiting respiratory syncytial virus infection

The present application relates to immunogens of broadly neutralizing monoclonal antibodies specific for HIV-1, such as broad and potent neutralizing monoclonal antibodies specific for HIV-1 and their gernation and methods of use. Broad neutralization suggests that the antibodies can neutralize HIV-1 isolates from different individuals. Immunogens or vaccines which may elicit such antibody associated responses are useful in pharmaceutical compositions for the prevention and treatment of HIV, and for the diagnosis and monitoring of HIV infection.

Immunogens of HIV-1 broadly neutralizing antibodies, methods of generation and uses thereof

Epitope-scaffold immunogens against respiratory syncytial virus (RSV)

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Encinitas, CA, United States of America

William Ray Schief