Seminar: Targeting HIV-1 with Glycoconjugate Vaccines: New Strategies for Antibody Induction against Viral Sugars

Abstract: In the ongoing fight against HIV-1, the dense glycosylation of the virus's envelope proteins presents both a challenge and a target for vaccine design. This presentation will explore innovative glycoconjugate strategies to evoke specific antibody responses to the sugars on the HIV-1 envelope spike. Recent studies highlight the potential of synthetic glycoconjugates to mimic the natural glycosylation patterns of HIV-1, which are typically not recognized by the human immune system due to their host-cell origin. We have developed glycoconjugates that closely resemble the HIV-1 glycan shield by employing molecular mimicry. Key findings include the design of synthetic derivatives of a bacterial lipooligosaccharide that bears a structural resemblance to the oligomannose clusters on HIV-1. These derivatives have shown promise in binding broadly neutralizing antibodies (bnAbs) and inducing specific immune responses in transgenic mouse models expressing human antibodies. Our results demonstrate that these glycoconjugate vaccines can bind to and potentially neutralize HIV-1 by targeting its glycan shield, offering a promising pathway for developing effective HIV vaccines. This seminar will detail the synthetic approaches, immunological outcomes, and future directions of this glycoconjugate-based vaccine strategy.