COVID-19 Nasal Vaccine Candidate Effective at Preventing Disease Transmission
By Laurie Fickman, University of Houston
September 15, 2021 - Breathe in, breathe
out. That’s how easy it is for SARS-CoV-2, the virus that causes COVID-19, to
enter your nose. And though 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 yet – like a nasal
vaccine – has been approved to provide mucosal immunity in the nose, the first
barrier against the virus before it travels down to the lungs.
But now, we’re one step closer.
Navin Varadarajan, University of Houston
M.D. Anderson Professor of Chemical and Biomolecular Engineering, and his
colleagues, are reporting in iScience the development of an intranasal subunit
vaccine that provides durable 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 immunization of large populations,” said Varadarajan.
“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
collaborated with Xinli Liu, associate professor of pharmaceutics 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)
within liposomal particles to yield the adjuvant named 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 significantly different physical and
chemical properties to the conventional adjuvant,” said Liu.
“We used NanoSTING as the adjuvant for
intranasal vaccination and single-cell RNA-sequencing to confirm the
nasal-associated lymphoid tissue as an inductive site upon vaccination. Our
results show that the candidate vaccine formulation is safe, produces rapid
immune responses - within seven days - and elicits comprehensive immunity
against SARS-CoV-2," said Varadarajan.
A fundamental limitation of
intramuscular vaccines is that they are not designed to elicit mucosal
immunity. As prior work with other respiratory pathogens like influenza has
shown, sterilizing immunity to virus re-infection requires adaptive immune
responses in the respiratory tract and the lung.
The nasal vaccine will also serve to
equitably distribute vaccines worldwide, according to the researchers. It is
estimated that first world countries have already secured and vaccinated
multiple intramuscular doses for each citizen while billions of people in
countries like India, South Africa, and Brazil with large outbreaks are
currently not immunized. These outbreaks and viral spread are known to
facilitate viral evolution leading to decreased efficacy of all vaccines.
“Equitable distribution requires
vaccines that are stable and that can be shipped easily. As we have shown, each
of our components, the protein (lyophilized) 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 novel intranasal
vaccines and therapies to help patients defeat debilitating diseases, including
COVID-19. The company has an exclusive license agreement with UH with respect
to the intellectual property covering intranasal vaccines and STING agonist
technologies. They have initiated the manufacturing process and plan to engage
the FDA later this year.
Along with Liu, Varadarajan’s team
includes postdoctoral researchers Xingyue An, Melisa Martinez-Paniagua;
research assistants Ali Rezvan, Mohsen Fathi and Sujit Biswas; doctoral student
Samiur Rahman Sefat, all from the University of Houston; and Shailbala Sing,
postdoctoral researcher at University of Texas M. D. Anderson Cancer Center;
Melissa Pourpak, BD; and Cassian Yee, M.D., University of Texas M. D. Anderson
Cancer Center.
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