Non-Viral COVID-19 Nasal Vaccine Candidate Effective at Preventing Disease Transmission

In Through The Nose…COVID-19 Nasal Vaccine Candidate Effective In Preventing Disease Transmission. Credit: University of Houston

Non-viral vaccine induces immunity in the respiratory tract.

Breath in breath out. That’s how easily SARS-CoV-2, the virus that causes COVID-19, can enter your nose. And while remarkable progress has been made in developing intramuscular vaccines against SARS-CoV-2, such as the readily available Pfizer, Moderna, and Johnson & Johnson vaccines, nothing — like a nasal vaccine — has yet been approved to boost mucosal immunity in the nose, the first barrier against the virus before it travels to the lungs.

Navin Varadarajan, professor of chemical and biomolecular engineering at the University of Houston, MD Anderson, reports that a nasal vaccine candidate for COVID-19 is effective in preventing disease transmission. Credit: University of Houston

But now we are one step closer.

Navin Varadarajan, MD Anderson, professor of Chemical and Biomolecular Engineering at the University of Houston, and colleagues report in iScience the development of an intranasal subunit vaccine that provides durable local immunity against inhaled pathogens.

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

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

“Our results demonstrate that the vaccine candidate formulation is safe, produces rapid immune responses – within seven days – and elicits comprehensive immunity against SARS-CoV-2.”
– Navin Varadarajan, lead author of the study

“NanoSTING has a small particle size of about 100 nanometers that exhibits significantly different physical and chemical properties than the conventional adjuvant,” Liu said.

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

“A fair distribution requires vaccines that are stable and easy to ship.”
— Navin Varadarajan, co-founder of AuraVax Therapeutics Inc.

A fundamental limitation of intramuscular vaccines is that they are not designed to elicit mucosal immunity. As previous work with other respiratory pathogens such as influenza has shown, sterilizing immunity against re-infection of the virus requires adaptive immune responses in the airways and lungs.

According to the researchers, the nasal vaccine will also serve to distribute vaccines fairly worldwide. It is estimated that first world countries have already secured and vaccinated multiple intramuscular doses for every citizen, while billions of people in countries like India, South Africa and Brazil with major outbreaks are currently unimmunized. These outbreaks and viral spread are known to facilitate viral evolution leading to reduced efficacy of all vaccines.

UH professor of engineering Navin Varadarajan (L) and professor of pharmacy Xinli Liu (R) are working together to develop a COVID-19 inhalation vaccine. Credit: University of Houston

“A fair distribution requires vaccines that are stable and easy to ship. As we have shown, each of our components, the protein (freeze-dried) and the adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing,” said Varadarajan.

Varadarajan is co-founder of AuraVax Therapeutics Inc., a pioneering biotech company developing new intranasal vaccines and therapies to help patients beat debilitating diseases, including COVID-19. The company has an exclusive licensing agreement with UH regarding the intellectual property of intranasal vaccines and STING agonist technologies. They have started the manufacturing process and plan to call in the FDA later this year.

Reference: “Single-dose intranasal vaccination elicits systemic and mucosal immunity to SARS-CoV-2” By Xingyue An, Melisa Martinez-Paniagua, Ali Rezvan, Samiur Rahman Sefat, Mohsen Fathi, Shailbala Singh, Sujit Biswas, Melissa Pourpak, Cassian Yee, Xinli Liu and Navin Varadarajan, September 24, 2021, iScience.
DOI: 10.116/j.isci.2021.103037

In addition to Liu, Varadarajan’s team includes postdoctoral researchers Xingyue An, Melisa Martinez-Paniagua; research assistants Ali Rezvan, Mohsen Fathi and Sujit Biswas; PhD student Samiur Rahman Sefat, all of the University of Houston; and Shailbala Sing, a postdoctoral researcher at the University of Texas MD Anderson Cancer Center; Melissa Pourpak, BD; and Cassian Yee, MD, University of Texas MD Anderson Cancer Center.