Skip to main content

Intranasal vaccines and COVID-19

Lindsay Dixon

Researchers at Yale School of Medicine have just completed a big study on the use of intranasal vaccines for COVID-19. These aren’t just any vaccine; they are a novel way to stimulate both local (mucosal) immunity as well as systemic immunity, and this could change the way we approach not only future COVID-19 vaccines, but also other vaccines such as Influenza, RSV, and even Cystic Fibrosis.

This study is a pre-print and has not yet been peer reviewed.

As much as the intramuscular mRNA vaccines have been a massive scientific breakthrough and initially performed even better than we had hoped prior to the clinical trials, the challenge has been that with every new variant, the ability to reduce infection and transmission has decreased significantly. A vaccine that reduces not only severe disease, but also infection would be incredibly beneficial in keeping the virus at bay.

The advantages of using an intranasal vaccine are many (including convenience, and ease of administration - especially for those with any type of needle phobia), and if this study goes according to plan, it will increase our ability to quickly produce new vaccines that are specific to the current circulating variant, while stimulating cross-reactive immunity both locally (in the respiratory mucosa) and systemically.

There have, however, been some significant barriers to more widespread use of intranasal vaccines (such as Flumist, i.e., a vaccine that many provinces currently use for influenza). In order to stimulate an appropriate immune response, intranasal vaccines cannot be used for immunocompromised people as they are "live attenuated" vaccines and are not safe for this population. Inert antigens, on the other hand, do not stimulate an appropriate immune response with this type of delivery system. The use of an adjuvant would assist in strengthening the immune response and overall efficacy of such vaccines but adjuvants are not safe for intranasal administration.

The research team at Yale, led by Dr. Akiko Iwasaki, is studying a novel approach known as Prime and Spike. Their research, carried out in mice, initially uses an IM injection of Pfizer’s mRNA lipid nanoparticle to “prime” the body’s immune system (they did note that without “priming” via IM mRNA, there was not an adequate immune response, hence this method is dependent on the initial “prime” of intramuscular mRNA). Weeks later they tested the intranasal use of an unadjuvanted recombinant “S” protein, as well as spike mRNA encapsulated in an immune-silent nanoparticle called Poly(amine-co-ester) (PACE). According to Dr. Iwasaki, “[t]he simple purified spike protein (in stabilized prefusion confirmation) was able to boost nasal, lung and serum IgA/IgG & resident memory B & ASC following an IM Pfizer mRNA prime.” The latter was also effective and produced mucosal antibodies, as well as other tissue-resident memory cells and biological response modifiers (BRM) showing that either of these approaches was successful at boosting both local and systemic immunity.


Lindsay Dixon illo

The researchers were able to show that Prime & Spike conveyed very protective immunity against severe disease and was also, importantly, able to significantly reduce the viral load. In addition, “Because Prime & Spike also establishes tissue-resident memory T and B cells, this strategy is likely to confer long-lasting and cross-reactive memory that can be quickly restimulated to prevent viral spread”, said Dr. Iwasaki.

Next steps are to test this approach in larger animals, and then in humans.  Xanadu Bio, a Yale University spinout, has recently secured an exclusive license from the school for a polymeric nanoparticle delivery platform to support the project. 

As the scientific community works to develop new ways to prevent the spread of infectious diseases like COVID-19 in our communities, the advent of an intranasal vaccine for COVID-19 that has good stability, helps to overcome the hesitancy of those who are needle-phobic, and can significantly curb infection and transmission, while also providing systemic cross-reactivity to address the inevitable appearance of new variants of SARS-CoV-2 is indeed very promising.

Lindsay Dixon is a Registered Pharmacist from British Columbia and is also the founder of an educational media platform called Friendly Pharmacy 5 where she uses video to explain complex scientific topics to healthcare professionals and the general population. For her recent video on the Yale Nasal Vaccine Study, as well as other videos on relevant health topics, check out her channel here:



Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses:

Mucosal vaccines — fortifying the frontiers:

Immune response:

Exploiting Mucosal Immunity for Antiviral Vaccines:

Unadjuvanted intranasal spike vaccine booster elicits robust protective mucosal immunity against sarbecoviruses:

Nasal Spray Booster Keeps COVID-19 at Bay:

Exploiting Mucosal Immunity for Antiviral Vaccines:

SARS-CoV-2 infection and persistence throughout the human body and brain:



This ad will auto-close in 10 seconds