Pharmacokinetic-pharmacodynamic modeling of a highly potent and broadly neutralizing anti-CD4 trimeric nanobody to inhibit HIV-1 infection

HIV-1 continues to pose a global health crisis, with millions of individuals depending on lifelong antiretroviral therapy, which faces significant challenges such as drug resistance and adherence issues. Nanobodies, which are small antibody fragments, present a promising alternative due to their high specificity, stability, and ease of production. Our study introduces Nb457-NbHSA-Nb457, a novel trimeric nanobody engineered to block HIV-1 entry by binding to CD4, the primary receptor for the virus. Using advanced pharmacokinetic-pharmacodynamic modeling, we predict the behavior of this therapy in humans, effectively bridging preclinical findings to clinical application. This research not only advances a new class of HIV therapeutics but also establishes a framework to expedite the development of nanobody-based drugs for infectious diseases, offering hope for simpler and more effective treatments to combat the pandemic.