(530e) Targeted Liposomal Therapeutic Vaccines for HIV

HIV remains a major public health issue in the US, with thousands of new infections every year. While advancements in anti-retroviral therapies (ART) have increased patient lifespans, ART does not cure HIV infection, leaving patients reliant upon ARTs. Here, we propose a new strategy for therapeutic HIV vaccines, the Nanotrap Therapeutic Vaccine (NTV). NTVs are modified liposomes consisting of HIV targeting molecules that bind gp120 and adjuvants that stimulate innate immune responses. This is essentially a targeted adjuvant which can improve initial immune responses to HIV. NTVs are designed to be injected after HIV infection, but concurrent with ART therapy when circulating viral loads are high. NTV will bind circulating HIV and be phagocytosed by local APCs, thereby co-delivering both HIV viral particle and adjuvant to APCs, activating them.

While the overall goal of developing NTVs is to generate early and potent anti-HIV responses, in this pilot study, we have data showing the initial validation of NTVs. First, we have shown that NTVs can bind and facilitate HIV psuedoviruses uptake by local APCs. We have selected three gp120 fusion inhibitors, typically used to inhibit HIV viral entry, which we displayed them on liposomal surfaces, verified that these liposomes bind HIV and inactivate the virus from infecting other cells using SPR and in vitro infection assays. Second, we have demonstrated that HIV pseudovirus can be captured in vivo using simple mouse models and be uptaken by murine innate immune cells. This project is innovative because NTVs can generate immune responses specific to the circulating virus in each patient, overcoming HIV’s high mutability evasion strategy. If successful, this proposal would generate a new class of HIV vaccine which could reduce patient reliance upon continual ART.