Unique sequences eliciting broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) that could be used to develop effective mRNA-based and other types of HIV vaccine. Problem: Despite decades of research, there is currently no vaccine to prevent HIV infection. A major goal of HIV vaccine programs is to generate bNAbs, which broadly bind to proteins on the outer surface of the virus and can neutralize diverse HIV strains. This is critical as HIV is known for its high variability and ability to evade the immune system. Solution: Engineered HIV surface proteins were tested in monkeys and found to elicit potent levels of bNAbs against multiple diverse strains of HIV. This is the first example of the consistent elicitation of bNAbs in any outbred animal model. These surface protein sequences can be used to design a potentially efficacious HIV vaccine. Technology: The inventors engineered mutations into the HIV envelope glycoprotein expressed on the surface of the virus. A version of HIV adapted for monkeys expressing the mutated envelope glycoproteins was tested to identify mutations that efficiently caused priming, boosting, and antibody affinity maturation of B cell precursors to produce bNAbs. When used to immunize monkeys, the mutated envelope glycoprotein elicited broad and potent bNAbs as early as 16-24 weeks post infection and at a far higher frequency than with the native envelope glycoprotein. Advantages:
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Docket # 24-10697