Methods and nucleic acid molecules for aav vector selection
US-2024417717-A1 · Dec 19, 2024 · US
US11248027B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-11248027-B2 |
| Application number | US-201715844753-A |
| Country | US |
| Kind code | B2 |
| Filing date | Dec 18, 2017 |
| Priority date | Jun 17, 2015 |
| Publication date | Feb 15, 2022 |
| Grant date | Feb 15, 2022 |
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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.
Opening claim text (preview).
What is claimed is: 1. A non-naturally occurring protein comprising a monomeric engineered outer domain (eOD), wherein the protein comprises SEQ ID NO: 10 (eOD-GT8). 2. The protein according to claim 1 , further comprising a tag for purification or biotinylation. 3. The protein according to claim 2 , wherein the tag for purification is a his tag. 4. The protein according to claim 2 , wherein the tag for biotinylation is an avi-tag. 5. The protein according to claim 1 , further comprising an additional cysteine, whereby the cysteine is configured for chemical conjugation.
transferring alkyl or aryl groups other than methyl groups (2.5) · CPC title
Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title
6,7-Dimethyl-8-ribityllumazine synthase (2.5.1.78) · CPC title
Murine · CPC title
Knock-in vertebrates, e.g. humanised vertebrates · CPC title
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