Research Projects

The Sustained Long-Acting Protection from HIV (SLAP HIV) program, funded by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), is an interdisciplinary project that aims to invent, develop and test a drug delivery system of a fourth-generation antiretrovirals (ARV) to protect high-risk individuals from HIV infection for up to a year. The SLAP HIV program supports teams exploring reservoir implants, degradable implants, and controlled release injectables for various ARV drugs, including Cabotegravir. In addition to comparing these systems functionally for stability, manufacturability, duration, and pharmacokinetic and safety endpoints, the program works in parallel with high-risk groups to understand their needs and preferences for the PrEP product.

The SLAP-HIV program is centered at Northwestern University, but includes researchers from across the US to advance the goal of developing a long acting formulation and advancing it through a phase 1 clinical trial. The SLAP-HIV team brings together broad expertise in multiple disciplines of HIV research to achieve the goals of the program.

The impact of the product platforms developed from this research has the potential to extend beyond HIV PrEP and can advance our understanding of how to implement long-acting HIV therapy for those already infected, and to other therapeutic areas where long-acting systems are needed.

The "Role of Myeloid Cells in CNS and Systemic Reservoirs and Rebound" project, funded by NIH, aims to characterize, using PET-CT technology, the eclipse phase of viral rebound as well as determine the impact of myeloid cell perturbation on rebound kinetics and dynamics in a rhesus macaque model after 1 year of combined antiretroviral therapy.

The project team includes researchers from Northwestern University and University of Louisiana at Lafayette. The techniques and methods derived from the study sites allow for localization of SIV active viremia sites in infected macaques to perform a detailed identification of the cells and anatomical compartments that support rebound of persistent SIV.

Given the importance of persistent viral populations in rebound, a better understanding of rebound virus population dynamics after analytic treatment interruption (ATI) is key to developing successful strategies to cure HIV-1.

The "Unraveling the Mechanisms of HIV Persistence and Rebound" program, funded by NIH, consists of 3 independent, although highly interconnected projects aligned to define the mechanisms of SIV persistence during viremia-suppressing combined antiretroviral therapy (cART) and early events in tissues during an analytic treatment interruption (ATI) with PET-CT guided necropsies. Specifically, the program aims to quantify and map the reservoir formation in the context of cART initiation, address the functional viral reservoir following prolonged cART with and without immune interventions designed to allow for transient viral replication, and finally, investigate the role of such interventions on the reservoir dynamic and composition upon ATI.

The program brings together the researchers from Northwestern University and University of Louisiana at Lafayette equipped with tools and broad expertise in different areas of HIV research to investigate and understand the role that different HIV target cells play, including mast cells, in the dynamics of the viral reservoir establishment and maintenance.

A better understanding of the mechanisms that govern HIV reservoir dynamics over time is essential to inform the development of strategies to cure HIV or control viral infection to overcome the need for life-long antiretroviral therapy.

Accelerating the Development of Vaccines and New Technologies to Combat the AIDS Epidemic (ADVANCE) program, funded by USAID, and in collaboration with the International AIDS Vaccine Institute (IAVI) and Moderna, aligns the latest scientific, technological and collaborative innovations to expedite the translation of scientific advancements into life-saving vaccines and other new prevention products. ADVANCE links African and Indian researchers with global collaborators and innovative technologies throughout all stages of HIV vaccine discovery, design and development.

As a part of ADVANCE program, Northwestern University works closely with University of Nairobi and Nairobi Institute of Primate Research to investigate the in vivo distribution and localization of IV injected antibodies and liposome delivered expressing mRNA, delineate the mucosal immune response induced by mRNA delivered ebNAbs, and establish the African Green Monkey as a new model for ebNAbs and HIV vaccine studies.

It is envisioned that the study findings of the collaborative research will contribute to determination of the efficacy and feasibility of use of ebNAbs for HIV prevention and treatment.

The "Characterizing mucosal changes in the female reproductive tract leading to increased HIV acquisition in Kenya after collecting both hysterectomy tissues and cervical secretions" project, funded by NIH, is a critical research effort aimed at advancing understanding of the factors contributing to increased susceptibility to HIV acquisition in individuals. The study aims to investigate the changes in the mucosal tissues of the female reproductive tract (FRT) and their correlation with increased risk of HIV acquisition. It examines hysterectomy-derived cervical tissues and mucus donated by high-risk populations in Nairobi, Kenya to gain insight into the changes in the mucosal system that alters epithelial and mucus barrier function.

The project is a collaborative effort between researchers from Northwestern University and University of Nairobi.

"Impact of Antibody Effector Function Diversity on Antiviral Activity In Situ" program, funded by NIH and in collaboration with Duke University and University of Louisiana at Lafayette, focuses on defining how antibody Fc-FcR mediated immunity can be used for preventing HIV infection and stopping infection in situ. Specifically, our laboratory aims to define the in vivo recognition of SIV/SHIV-infected cells by antibody and FcR-bearing cells in the gastrointestinal (GI) and female reproductive tract (FRT) mucosae by utilizing a novel system that leverages tagged antibodies and correlative PET/CT as a beacon for targeted mucosal tissue sample collection at necropsy in SIV/SHIV-infected rhesus macaques (RM) to characterize events in foci of early viral replication in the mucosae.

The "Cheetah Center for the Structural Biology of HIV Infection" project, funded by NIH, aims to advance the understanding of HIV-host interactions, and provide the foundations for developing new therapeutic strategies for HIV treatment and cure. Our laboratory’s goal within this collaborative project is to characterize and modulate HIV dynamics via whole-animal studies focused on imaging and characterization of sites of viral rebound at the cellular and tissue levels as well as structural studies of proviral silencing and reactivation. We are also involved in the studies that attempt to create new pantropic blocks to enveloped virus budding and new biologics delivery systems.

The project is a collaborative effort between researchers from Northwestern University and University of Utah.

The "Functionally Defining HIV-Host Interactions During the Early HIV-1 Lifecycle" project, funded by NIH, is a collaborative research effort led by the Hope Laboratory which bridges expertise in virology, cell biology, and imaging technologies to address longstanding questions surrounding the early stages of HIV-1 infection and aims to unravel the complexities of early HIV-1 infection dynamics. Through the multi-institutional effort, the team of experts from institutions including the Northwestern University, Rockefeller University, Salk Institute for Biological Studies, University of Pittsburgh, and Rush University, seeks to define the infectious pathway of HIV-1 from fusion to integration in optimized cell culture models and primary human cells and determine the role of host permissivity factors and viral components in early HIV-1 infection.

The project utilizes cutting-edge technologies such as cryo-EM, super-resolution fluorescence microscopy, CRISPR-Cas9 gene editing, and single-particle tracking to dissect and define the interactions, kinetics, and dynamics between viral and host factors that drive productive infection.

Gaining mechanistic insights into the intricate processes underlying HIV-1 pathogenesis by integrating molecular imaging approaches to visualize viral-host interactions at the single-particle level, plays an important role in paving the way for the development of more effective therapies for HIV-1 treatment and prevention.