COVID-19 nasal vaccine candidate effective in preventing disease transmission

Inhale, breathe. It is so easy for SARS-CoV-2, the virus that causes COVID-19, to enter the nose. And while significant progress has been made in the development of intramuscular SARS-CoV-2 vaccines, such as the easily accessible Pfizer, Moderna, and Johnson & Johnson vaccines, nothing has yet been approved — such as a vaccine. nasal— to provide mucous immunity to the nose. , the first barrier against the virus before traveling to the lungs.

But now we are one step closer.

Navin Varadarajan, Professor of Chemical and Biomolecular Engineering, MD Anderson, University of Houston, and colleagues report to iScience the development of a subunit intranasal vaccine that provides lasting local immunity against inhaled pathogens.

“Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a suitable non-invasive procedure for vaccination of large populations,” Varadarajan said. “However, mucosal vaccination has been hampered by the lack of efficient antigen delivery and the need for appropriate adjuvants that can stimulate a robust immune response without toxicity.”

To solve these problems, Varadarajan collaborated with Xinli Liu, an associate professor of pharmaceuticals at UH College of Pharmacy and an expert in nanoparticle delivery. Liu’s team was able to encapsulate the interferon gene stimulator (STING) agonist inside liposomal particles to obtain the adjuvant called NanoSTING. The function of the adjuvant is to promote the body’s immune response.

“NanoSTING has a small particle size around 100 nanometers, which exhibits physical and chemical properties significantly different from those of conventional adjuvant,” Liu said.

“We used NanoSTING as an adjuvant for intranasal vaccination and monocellular RNA sequencing to confirm nasal-associated lymphoid tissue as an inductive site after vaccination. Our results show that the candidate vaccine formulation it is safe and produces rapid immune responses, within seven days and causes complete immunity against SARS-CoV-2, ”Varadarajan said.

A fundamental limitation of intramuscular vaccines is that they are not designed to cause mucosal immunity. As demonstrated in previous work with other respiratory pathogens such as influenza, sterilizing immunity to virus reinfection requires adaptive immune responses to the airways and lungs.

The nasal vaccine will also serve to distribute vaccines equitably around the world, according to the researchers. It is estimated that first world countries have already secured and vaccinated multiple intramuscular doses for each citizen, while currently billions of people in countries such as India, South Africa and Brazil with major outbreaks are not immunized. These outbreaks and viral spread are known to facilitate viral evolution leading to a decrease in the efficacy of all vaccines.

“Equitable distribution requires stable, easily deliverable vaccines. As we have shown, each of our components, protein (lyophilized) and adjuvant (NanoSTING) are stable for more than 11 months and can be stored and shipped without freezing.” , said Varadarajan.

Varadarajan is a co-founder of AuraVax Therapeutics Inc., a pioneering biotechnology company that develops new vaccines and intranasal therapies to help patients defeat debilitating diseases, including COVID-19. The company has an exclusive licensing agreement with UH regarding the intellectual property that covers intranasal vaccines and STING agonist technologies. They have begun the manufacturing process and plan to contract with the FDA later this year.