At the NIAID Vaccine Research Center, the PREMISE (Pandemic REsponse REpository through Microbial and Immune Surveillance and Epidemiology) program was established to support pandemic preparedness and response. Through a network of investigators and collaborators, PREMISE conducts virologic and immunologic screening of targeted and broad cohorts to detect reactivity against pathogens of pandemic potential. PREMISE also sequences samples from animal reservoirs and symptomatic humans to identify new and re-emerging pathogens. The resulting analyses are shared to pre-emptively generate reagent and data resources for early detection and diagnosis, and to identify monoclonal antibodies and immunogens for vaccine and therapeutic discovery and development. Ultimately, PREMISE aims to serve as a translational vehicle to integrate serologic and cellular immune discovery, targeting a broad array of pathogens, into product development for pathogens with pandemic potential.

The PREMISE initiative and its partnerships

Credit: NIAID

Philosophy - Advancing Human Health Through Immunological Research:

• Enhance understanding of immune system regulation in health and disease
• Provide mechanistic insights into disease pathology to inform therapeutic strategies
• Support translational research to develop targeted treatments for immune-related disorders

Secondary Lymphoid Organ Remodeling and Pathogen-Immune cell Interactions:

• Investigate structural remodeling of lymph nodes in immune responses
• Examine chemokine receptor sensitivity modulation by RGS proteins
• Characterize cellular networks facilitating virus envelope protein transfer

Extracellular Signaling, GPCR Signal Transduction and Immune Modulation:

• Investigate chemokine receptor-mediated signaling in immune cell regulation
• Examine heterotrimeric G-protein activation in lymphocyte function
• Study molecular mechanisms of G-protein-coupled receptor (GPCR) signaling
• Analyze how GPCR signaling orchestrates immune responses and cell dynamics

Experimental Approaches:

• Utilize genetically engineered murine models
• Employ intravital two-photon laser scanning microscopy (TP-LSM) and high-throughput flow cytometry

The Neurovirology Unit conducts research on the acute and long-term complications associated with human alphaherpesvirus infections and pulmonary infections caused by coronaviruses and influenza.

Using transgenic animal models and integrating approaches from molecular virology, neurobiology, and immunology, we investigate the mechanisms underlying viral pathogenesis in the central nervous system, which particularly involves analyzing roles of immunomodulatory host factors to understand their roles in pathogenesis, neuroprotection, and potentiating antiviral immunity. While studying different aspects of antiviral immunity, we also focus on understanding the neurological regulation of antiviral immunity, neuroinflammation, and the long-term manifestations of viral infection, such as neurodegeneration and cognitive decline using machine learning-based behavioral approaches.

Additionally, the Neurovirology Unit explores the interactions between viral proteins, host factors, and immune responses that drive differential disease severity observed in humans, paving the way for innovative therapeutic strategies. We are also committed to advancing human brain and lung organoid models to recapitulate disease phenotypes in humans and thereby enhance our understanding of viral disease mechanisms.

Our research focuses on the complex interactions between the human immune system and insect-derived molecules, and how these interactions can influence the outcomes of vector-borne diseases such as dengue, Zika, Chikungunya, and leishmaniasis. When an insect bites, it injects hundreds of arthropod molecules into the host's skin, alerting our immune system to these foreign agents. If the insect is infected with a pathogen, the microorganism is delivered along with these insect-derived molecules. Our immune response to these molecules over time can either help or hinder pathogen establishment, ultimately affecting the disease outcome.

Our work is conducted at two primary locations: the Laboratory of Malaria and Vector Research (LMVR) in Rockville, which is equipped with cutting-edge technologies, and the NIAID International Center of Excellence in Research (ICER) in Cambodia, where we conduct field observations and studies.

At LMVR-Rockville, we use advanced technologies and methodologies to explore the molecular and immunological mechanisms underlying the human response to arthropod bites and the pathogens they transmit. In Cambodia, at the NIAID ICER, we engage in extensive fieldwork to gather critical data and observations directly from affected populations. By integrating field data with laboratory findings, we aim to develop robust hypotheses that can lead to effective strategies for disease mitigation and control.

Our multidisciplinary approach allows us to bridge the gap between laboratory research and field applications. By understanding how the human immune system responds to arthropod molecules, we can identify potential targets for vaccines, therapeutics, and diagnostic tools. Additionally, our research contributes to the development of innovative vector control strategies that can reduce the incidence of these debilitating diseases.

Through collaboration with local communities, healthcare providers, and international partners, we strive to translate our scientific discoveries into practical solutions that can improve public health outcomes. Our ultimate goal is to reduce the burden of vector-borne diseases and enhance the quality of life for people living in endemic regions.

Our research aims to improve dengue prevention and treatment strategies for U.S. travelers, personnel in endemic areas, and regions with reported dengue cases, such as Hawaii, Florida, Texas, Puerto Rico, the U.S. Virgin Islands, and Guam. Enhanced predictive, management, diagnostic, and preventive measures for dengue outbreaks are particularly crucial for these at-risk regions. The development and use of prophylactic therapeutics targeting specific immune responses to mosquito bites could reduce the transmission of arboviruses, including eastern equine encephalitis, Jamestown Canyon, La Crosse, Powassan, St. Louis encephalitis, and West Nile viruses. Improved diagnostic capabilities for vector-borne diseases and emerging infections will lead to better patient outcomes.