Inhale Exhale. This is how easy it is for SARS-CoV-2, the virus that causes COVID-19, to get into your nose. And while remarkable progress has been made in the development of intramuscular SARS-CoV-2 vaccines, such as the readily available Pfizer, Moderna, and Johnson & Johnson vaccines, nothing yet – like a nasal vaccine – has been approved to provide mucosal immunity in the nose, the first barrier against the virus before it descends to the lungs.
But now we are one step closer.
Navin Varadarajan, professor of chemical and biomolecular engineering at the University of Houston MD Anderson, and colleagues, report in iScience the development of an intranasal subunit vaccine that provides long-lasting local immunity against inhaled pathogens.
“Mucosal vaccination can stimulate both systemic and mucosal immunity and has the advantage of being a non-invasive procedure suitable for immunizing large populations,” Varadarajan said. “However, mucosal vaccination has been hampered by the lack of efficient antigen delivery and the need for appropriate adjuvants which can stimulate a robust immune response without toxicity.”
To address these issues, Varadarajan collaborated with Xinli Liu, associate professor of pharmacy at UH College of Pharmacy and expert in nanoparticle administration. Liu’s team were able to encapsulate the interferon gene stimulator (STING) agonist in liposomal particles to produce the adjuvant called NanoSTING. The function of the adjuvant is to promote the body’s immune response.
âNanoSTING has a small particle size of around 100 nanometers which exhibits very different physical and chemical properties than conventional adjuvant,â Liu said.
âWe used NanoSTING as an adjuvant for intranasal vaccination and single-cell RNA sequencing to confirm lymphoid tissue associated with the nose as an inductive site during vaccination. Our results show that the candidate vaccine formulation is safe, produces rapid immune responses – within seven days – and elicits complete immunity against SARS-CoV-2, âVaradarajan said.
A fundamental limitation of intramuscular vaccines is that they are not designed to induce mucosal immunity. As previous work with other respiratory pathogens like influenza has shown, sterilization of immunity against viral reinfection requires adaptive immune responses in the airways and lungs.
The nasal vaccine will also be used to distribute vaccines fairly around the world, the researchers say. It is estimated that first world countries have already obtained and vaccinated multiple intramuscular doses for every citizen while billions of people in countries like India, South Africa and Brazil with large epidemics are currently not immune . These epidemics and viral spread are known to facilitate viral evolution leading to a decrease in the effectiveness of all vaccines.
âEquitable distribution requires stable vaccines that can be shipped easily. As we have shown, each of our components, protein (lyophilized) and adjuvant (NanoSTING) are stable for over 11 months and can be stored and shipped without the need for freezing, âVaradarajan said.
Varadarajan is co-founder of AuraVax Therapeutics Inc., a pioneering biotechnology company developing new vaccines and intranasal therapies to help patients overcome debilitating diseases, including COVID-19. The company has an exclusive licensing agreement with UH with respect to intellectual property covering intranasal vaccines and STING agonist technologies. They’ve kicked off the manufacturing process and plan to engage the FDA later this year.
Reference: An X, Martinez-Paniagua M, Rezvan A, et al. Single dose intranasal vaccination elicits systemic and mucosal immunity against SARS-CoV-2. iScience. 2021; 24 (9). do I: 10.1016 / j.isci.2021.1103037.
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