Innovative nasal spray and vaccine for protection against respiratory viruses

A team of researchers led by the University of Houston has discovered two new ways to prevent and treat respiratory viruses. In back-to-back papers published in Nature Communications, the team—from the lab of Navin Varadarajan, MD Anderson’s William A. Brookshire Professor of Chemical and Biomolecular Engineering—reports the development and validation of NanoSTING, a nasal spray, as a broad-spectrum immune enhancer to control infection against multiple respiratory viruses; and the development of NanoSTING-SN, a pan-coronavirus nasal vaccine, which can protect against infection and disease from all members of the coronavirus family.

Therapeutic Highlights of NanoSTING

— NanoSTING, a nasal spray, can prevent many respiratory viruses by activating the immune system and preventing infection by viruses. It can also protect against reinfection with SARS-CoV-2.

— A single intranasal dose of NanoSTING was shown to be effective against SARS-CoV-2 and influenza virus strains.

— NanoSTING is complementary to vaccines and allows cells to be in a heightened state of alert to prevent attack by respiratory viruses.

Highlights of the pan-coronavirus vaccine NanoSTING-NS

— UH researchers have developed NanoSTING-SN, a nasal vaccine that prevents transmission to unvaccinated people and combats multiple COVID variants.

— NanoSTING-SN offers exciting potential towards a universal coronavirus vaccine and could end the cycle of viral transmission and evolution in immunocompromised individuals.

— Intramuscular vaccines prevent disease but are less effective at preventing infections. NanoSTING-SN may provide better protection against transmission of COVID variants and related sarbecoviruses.

NanoSTING

NanoSTING is a special formula that uses tiny fat droplets to deliver an immune-boosting ingredient called cGAMP. This formula helps the body’s cells stay on alert to prevent respiratory virus attacks.

Using multiple models, the team demonstrated that a single treatment with NanoSTING not only protects against pathogenic strains of SARS-CoV-2, but also prevents the transmission of highly transmissible variants such as the Omicron variants. Administering NanoSTING into the nose ensures that the immune system is activated in the nasal compartment, which in turn prevents infection by viruses.

Navin Varadarajan, MD Anderson, William A. Brookshire Professor of Chemical and Biomolecular Engineering

As the recent COVID-19 pandemic has shown, developing off-the-shelf treatments to combat respiratory viruses is a largely unsolved problem that has an enormous impact on human life.

“Our results showed that intranasal administration of NanoSTING is able to elicit beneficial responses to type I and type III interferons that are associated with immune protection and antiviral benefit,” reports first author and postdoctoral associate Ankita Leekha.

The authors further demonstrate that NanoSTING can protect against both Tamiflu-sensitive and Tamiflu-resistant influenza strains, highlighting its potential as a broad-spectrum therapy.

“The ability to activate the innate immune system presents an exciting avenue to protect humans against multiple respiratory viruses and viral variants, and also to minimize transmission to vulnerable individuals,” Leekha said. “The advantage of NanoSTING is that only one dose is required, unlike antivirals like Tamiflu that require 10 doses.”

NanoSTING’s mechanism of action is complementary to vaccines, monoclonal antibodies and antivirals, the authors noted.

Nano STING-SN

Despite the successful implementation of several SARS-CoV-2 vaccines, these vaccines require constant updates due to viral evolution, and the current generation of vaccines offers only limited protection against SARS-CoV-2 transmission.

Introducing NanoSTING-SN, a multi-antigen intranasal vaccine that eliminates virus replication in the lungs and nostrils and has the ability to protect against multiple coronaviruses and variants.

“Using multiple preclinical models, the team demonstrated that the vaccine candidate protects the primary host from disease when challenged with highly pathogenic variants. Significantly, the vaccine also prevents transmission of highly transmissible variants like the Omicron variants to vaccine-naïve hosts,” Varadarajan reports.

The authors further demonstrate that the nasal vaccine was 100% effective in preventing transmission of Omicron VOCs to unvaccinated hosts.

“The ability to protect against multiple coronaviruses and variants offers promising potential for a universal coronavirus vaccine,” Leekha said. “The ability to prevent infections and transmission could finally end this cycle of transmission and viral evolution in immunocompromised individuals.”

The research was conducted by a collaborative UH team including Xinli Liu of the College of Pharmacy and Vallabh E. Das of the College of Optometry, along with Brett L. Hurst of Utah State University and in consultation with AuraVax Therapeutics, a spinoff of Varadarajan’s Single Cell Lab at UH, which is developing NanoSTING.

Funding for the studies was provided by the NIH (R01GM143243), the Owens Foundation, and AuraVax Therapeutics.