STINGing viruses to engineer effective vaccines and therapeutics


Monday, May 23, 2022 - 9:00am


ESB 1001


Navin Varadarajan - University of Houston


Within the last 20 years, we experienced four global respiratory epidemics/pandemics: severe acute respiratory syndrome (SARS) in 2003, influenza H1N1 in 2009, Middle East respiratory syndrome coronavirus in 2012, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These pandemics added to the global burden of existing threats like seasonal Influenza and respiratory syncytial virus (RSV). The recent COVID-19 pandemic caused by SARS-CoV-2 has led to 6.17 million deaths (April 2022), while current outbreaks driven by new variants of concern (VOC’s) continue to be reported worldwide.

Humanity is in the middle of one of the largest vaccination campaigns trying to protect >7.5 billion people against coronavirus induced disease (COVID-19). The continued evolution of SARS-CoV-2 variants of concern (VOC) like the Omicron VOCs has caused massive increases in infections even in countries with high vaccination coverage. There are two issues with the current intramuscular vaccines: (1) they do not prevent viral infection in the upper-airways, and (2) they target exclusively the spike protein which while necessary might not be sufficient for sterilizing immunity. Here, we report the ability of intranasal vaccines adjuvanted with the liposomally encapsulated stimulator of interferon genes (STING) agonist, NanoSTING. We designed a multi-protein intranasal vaccine (NanoSTING-NS) that leads to a complete elimination of detectable viral loads in both the lungs (clinical disease) and the nostrils (transmission). Even a single dose of NanoSTING-NS is effective at significantly reducing transmission of the highly infectious SARS-CoV-2 Omicron VOC in hamsters. Collectively our data provide an immunization pathway to directly impact transmission  of even highly infectious variants and have important implications in understanding the quality of immunity elicited by natural infection in comparison to the current generation of vaccines.

Despite the amazing efficacy of the vaccines, they have disadvantages with regards to emerging or novel pathogens. Vaccines require significant time for identification and characterization of the virus, development, and rapid testing to identify the emerging pathogen, followed by manufacturing and global distribution of therapeutics or vaccines. With regards to rapidly mutating viruses such as the RNA viruses, vaccines are prone to failure due to the high mutation rate of the virus coupled with insufficient and ineffective protection, which facilitates the evolution of resistant variants. The availability of prophylactics or early post-exposure therapeutics (treatment initiated prior to clinical symptoms) that can both prevent disease and reduce transmission is an urgent and unmet clinical need. Using multiple animal models, we demonstrate that a single dose of intranasal NanoSTING can work as prophylactic and therapeutic against multiple respiratory viruses (and standard treatment-resistant variants). We envision NanoSTING as a treatment to prevent respiratory viral disease in vulnerable populations or to rapidly intervene in respiratory infections before etiology is determined.


Navin Varadarajan is the MD Anderson Professor at the William A. Brookshire Department of Chemical & Biomolecular Engineering at the University of Houston. His research is focused on human immunology and immunotherapy to enable the development of therapeutics and vaccines for diseases including rheumatoid arthritis, cancer, influenza and SARS-CoV-2. Navin has received numerous awards, including the first engineer to receive the Melanoma Research Alliance Young Investigator Award and the CDMRP Cancer Career Award. He has also been the recipient of several research and teaching awards, including the Faculty Teaching and Research Excellence Awards from the Cullen College of Engineering. He is an inventor on several patents; is the co-founder and CSO of CellChorus and AuraVax Therapeutics, and a senior member of the National Academy of Inventors.  

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