Innovative nasal sprays and vaccines for respiratory virus prevention

A University of Houston-led research team has discovered two new ways to prevent and treat respiratory viruses. In back-to-back papers published in Nature Communications, a team from the laboratory of Navin Varadarajan, the William A. Brookshire Professor of Chemical and Biomolecular Engineering at MD Anderson, reports the development and validation of a nasal spray, NanoSTING, as a broad-spectrum immune activator to control infections against multiple respiratory viruses, and the development of a pan-coronavirus nasal vaccine, NanoSTING-SN, that can prevent infection and disease from all members of the coronavirus family.

NanoSTING Therapeutic Highlights

— NanoSTING nasal spray can protect against multiple respiratory viruses by activating the immune system and preventing viral infections, and can also protect against reinfection with SARS-CoV-2.

–A single intranasal dose of NanoSTING has proven effective against strains of SARS-CoV-2 and influenza virus.

— NanoSTING could complement vaccines, keeping cells on alert to ward off respiratory viral attacks.

Highlights of the NanoSTING-NS Pan-Coronavirus Vaccine

— Researchers at the University of Hawaii have developed a nasal vaccine, NanoSTING-SN, that combats multiple COVID variants and prevents infection in unvaccinated individuals.

–NanoSTING-SN offers exciting potential for a universal coronavirus vaccine, potentially ending the cycle of viral transmission and evolution in immunocompromised people.

–Intramuscular vaccines prevent disease but are less effective at preventing infection. NanoSTING-SN can provide increased protection against infection with COVID variants and related sarbecoviruses.

Nanosting

NanoSTING is a special formulation that uses tiny lipid droplets to deliver an immune-boosting ingredient called cGAMP, which helps keep the body's cells on alert to ward off respiratory viral attacks.

Using multiple models, the research team demonstrated that a single treatment with NanoSTING not only protects against pathogenic strains of SARS-CoV-2, but also prevents infection with highly infectious variants like the omicron variant. By delivering NanoSTING to the nose, the immune system in the nasal cavity is activated, preventing viral infection.”

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

As the recent COVID19 pandemic has shown, the development of off-the-shelf treatments against respiratory viruses remains a largely unsolved problem with significant impact on human lives.

“Our findings showed that intranasal administration of NanoSTING can induce beneficial type I and type III interferon responses associated with immune protection and antiviral effects,” reports first author and postdoctoral researcher Ankita Leekha.

Furthermore, the authors showed that NanoSTING could protect against both Tamiflu-susceptible and -resistant influenza strains, highlighting its potential as a broad-spectrum therapeutic.

“The ability to activate the innate immune system offers an attractive approach to protect humans against multiple respiratory viruses and viral variants while also minimizing transmission to vulnerable populations,” Riecka said. “The advantage of nanoSTING is that only one dose is required, unlike antiviral drugs such as Tamiflu, which require 10 doses.”

The authors noted that NanoSTING's mechanism of action complements vaccines, monoclonal antibodies, and antiviral agents.

Nano STING-SN

Despite the successful introduction of multiple vaccines against SARS-CoV-2, these vaccines need to be continually updated due to viral evolution, and furthermore, the current generation of vaccines only provides limited protection against SARS-CoV-2 infection.

NanoSTING-SNantigenIntranasal vaccines have the ability to eliminate viral replication in both the lungs and nasal cavity and protect against multiple infections. coronavirus and its variants.

“Using multiple preclinical models, the team demonstrated that the vaccine candidate protects the primary host from disease upon exposure to highly pathogenic variants. Importantly, the vaccine prevents highly transmissible variants, such as the omicron variant, from being transmitted to unvaccinated hosts,” Varadarajan reports.

Furthermore, the authors show that the nasal vaccine is 100% effective in preventing transmission of Omicron VOC to unvaccinated hosts.

“The ability to protect against multiple coronaviruses and their variants offers exciting prospects for a universal coronavirus vaccine,” Riecka said. “The ability to prevent infection and transmission may finally put an end to the cycle of transmission and viral evolution in immunocompromised people.”

The research was conducted by a collaborative team from the University of Hawaii, including Brett L. Hurst of Utah State University, Xingli Liu of the University of Utah College of Pharmacy and Vallabh E. Das of the University of Utah College of Optometry, and was advised by AuraVax Therapeutics, a spin-off from Varadarajan's Single Cell Laboratory at the University of Hawaii, which is developing NanoSTING.

Funding for this research came from the NIH (R01GM143243), the Owens Foundation, and AuraVax Therapeutics.