The Scripps Research Institute

International Aids Vaccine Initiative

Daniel Kulp

William Ray Schief

Sergey V Menis

Joseph Graham Jardine

Bruno E Correia

Ron Jacak

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 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

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Daniel Kulp