Intranasal COVID-19 Vaccine May Be More Effective Than Injected Vaccines

Intranasal COVID-19 Vaccine May Be More Effective Than Injected Vaccines

There are more than 150 experimental COVID-19 vaccines under development around the world, all of which are being designed for intramuscular injection.1 Some researchers are investigating whether the conventional intramuscular injection route is less effective when using vaccines to prevent microbial infections that invade the respiratory airway like SARS-CoV-2.2

Avery August, PhD, an immunologist at Cornell University, said, “When we take apart and present pathogens in a way that the immune system doesn’t naturally see them, it’s not as ideal.” He adds, “You run the risk of not generating the right immune response.”3

Researchers are now exploring the option of developing an intranasal mucosal vaccine to prevent COVID-19.4

Why An Intranasal Vaccine for COVID-19 May Be More Effective

Researchers concerned about the potential ineffectiveness of COVID-19 vaccines administered intramuscularly speculate that a vaccine administered nasally would generate a stronger mucosal response and more protection against the acute respiratory infection caused by SARS-Cov-2.5

Researchers explain that many pathogens enter the body through the mucosa—the tissue that lines the nose, mouth, lungs and digestive tract—and trigger an immune response in that particular area of the body. Intramuscular vaccines are believed to do a poor job of triggering mucosal immune responses and must instead rely on immune cells mobilized from elsewhere in the body flocking to the mucosal tissue sites of the infection.6

Sarah Gilbert, PhD, vaccinologist at Oxford University in England, spoke on intranasal vaccines and said, “This takes the vaccine itself right down into the lungs where it can access the same tissue that would be reached by the virus infection.”7

Roadblocks in Developing an Intranasal Vaccine

There are several challenges to developing intranasal vaccines and developing vaccines that more effectively induce mucosal immunity has been challenging for researchers.8 For example, the live virus FluMist nasal spray vaccine licensed in the U.S for influenza contains an attenuated influenza virus and is believed to be more effective than inactivated injected influenza vaccines given intramuscularly in young children. However, the same influenza nasal vaccine has shown to be ineffective in adults.9 The live oral polio vaccine (OPV), which is used in other countries, has been linked to polio outbreaks when the attenuated virus in the product mutates and becomes pathogenic, causing vaccine strain polio paralysis in the person vaccinated or someone who comes in contact with a recently vaccinated person’s body fluids shedding the virus.10

Anna Durbin, MD, infectious disease researcher at John Hopkins University said that designing a mucosal vaccine with less risky ingredients such as inactivated viruses would make the nasal vaccine too weak to stimulate a long-term immune response. She states, “You want the vaccine to be strong enough to get in and do what it needs to do, but it can’t cause a lot of symptoms. It’s a really difficult balance.”11

Five Pharmaceutical Companies/Universities Developing Intranasal Vaccines

Currently, there are five pharmaceutical companies and universities in the U.S, Canada, Netherlands, Finland and India that are working on an intranasal vaccine for COVID-19, which the companies hope will offer protection at not only the mucosal site of the respiratory tract but also the intestines and genital tract.12

In the U.S, a biopharmaceutical company called Altimmune , in collaboration with DynPort Vaccine in Maryland, has developed an intranasal COVID-19 vaccine candidate known as AdCOVID. Researchers at the University of Waterloo in Canada are developing a DNA-based vaccine candidate that can be given via intranasal administration. Dutch research and development vaccine institute Intravacc, Wageningen Bioveterinary Research and Utrecht University are jointly developing an intranasal vaccine that uses a Newcastle disease virus (NDV) vector.13

Researchers at the University of Eastern Finland and the University of Helsinki are developing a COVID-19 vaccine that will be administered as a nasal spray using gene transfer technology and an adenovirus carrier. Bharat Biotech in India in collaboration with University of Wisconsin–Madison and vaccine firm FluGen, has also developed ‘CoroFlu’, a one-drop COVID-19 nasal vaccine.14


1 KuWu K. You’d Rather Get a Coronavirus Vaccine Through Your Nose. The New York Times  July 14, 2020.
2 Ibid.
3 Ibid.
4 Ibid.
5 Fonrouge G. Coronavirus vaccine may be stronger through nasal spray. New York Post June 23, 2020.
6 See Footnote 1.
7 See Footnote 5.
8 See Footnote 1.
9 See Footnote 1.
10 Ibid.
11 Ibid.
12 De A. Explained: How will Covid-19 nasal vaccines work, which firms are developing it? Indian Express July 16, 2020.
13 Ibid.
14 Ibid.

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