A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.
History Nasal inoculation dates as far back as the 17th century in China during the Kangxi Emperor's reign. Documentation during this period indicates that the Kangxi Emperor vaccinated his family, army, and others for mild smallpox. Manuals detailing vaccination techniques at the time all focused on sending smallpox up the nose of the individual being vaccinated. Although other vaccination techniques were developed using an infected individual's scabs, a common method was to place a cotton swab with the fluid from an infected person's pustule up the nose. Following smallpox, influenza became a prominent focus for nasal vaccine development. The first live attenuated influenza vaccine (LAIV) in the form of a nasal spray was created in Russia by the Institute of Experimental Medicine in 1987. This nasal vaccine development was based on the Russian backbone of LAIV while nasal vaccines since then have been based on other LAIV backbones. The first nasal influenza vaccine was released in the United States in 2001 but was taken off the market due to toxicity concerns. FluMist, one of the most prominent nasal LAIVs, was released in 2003 as nasal LAIVs continued developing.
Anthrax attacks at the beginning of the 21st century caused a demand for nasal vaccine development. As anthrax is an airborne substance that can be inhaled, a nasal vaccine has the potential to be used to protect individuals from the effects it can have on the respiratory system. Following the September 11, 2001 terrorist attacks in the United States, several individuals at news stations and U.S. senators died after being sent letters with anthrax as an act of bioterrorism. Nasal vaccine research and development against anthrax was encouraged by the U.S. government in an effort to vaccinate troops. BioThrax, the current anthrax vaccine that is licensed and administered in the United States, requires up to five intramuscular injections and annual boosters; research within the past decade has developed an alternative nasal vaccine that follows the path of infection for anthrax and induces both humoral and cellular immune responses. The global COVID-19 pandemic led to a rise in nasal vaccines against coronavirus. International efforts for vaccine development occurred as countries such as India, Iran, Russia, and China created nasal COVID-19 vaccines.
Administration
Nasal vaccines are a subsection of mucosal immunization as they use a mucosal route for vaccine delivery. As many pathogens can enter the body through the nose, nasal vaccines take advantage of this mechanism to deliver the vaccine. The nose has multiple lines of defense to prevent pathogens from entering further into the body. Nasal hairs are the first defense as they are at the entrance of the nose and prevent large particles from entering. The mucus layer in the nasal cavity can trap smaller particles that get past the nose hairs. The nasal cavity has a large vascularization network, allowing particles to go through the epithelial layer and directly enter the bloodstream. Intruding particles will interact with the mucosal immune system if they reach the nasal mucosa. The mucosal immune system is composed of lymphoid tissue, B cells, T cells, and antigen-presenting cells. These different types of cells work together to identify intruding particles and trigger an immune response. Nasal vaccines must overcome these barriers and get clearance to deliver the viral antigen to patients. Nasal vaccines can come in different forms such as solutions (liquids), powders, gels, and solid inserts. The most prevalent type of nasal vaccine in research and clinical application is solutions due to its ease of use. Although solutions are usually pipetted into test subjects' nostrils when conducting animal trials for nasal vaccines, nasal sprays are considered the most practical approach for mass human vaccination using nasal vaccines. A nasal spray is able to bypass the initial layers of the nasal mucosa and deliver the vaccine particles directly to the mucoadhesive layer. The antigen in the nasal vaccine can then trigger an immune response and prevent infection due to nasal vaccines' accessibility to the immune system. Nasal sprays are commonly used for delivering drugs in addition to vaccines. Decongestant drugs are often directly delivered to the nose through nasal sprays. Cold and allergy medication can be administered using nasal sprays for local delivery by bypassing nasal hairs and being introduced to the nasal cavity. Intranasal administration can have less drug degradation compared to oral administration because of direct particle delivery. Peptide drugs used for hormone treatments can be delivered nasally through nasal sprays instead of orally to retain particle integrity. Nasal sprays can also be used to deliver diabetes treatment, steroids, and intranasal oxytocin to induce labor. Nasal administration is also used to deliver anesthetics and sedatives due to direct access to the mucosal immune system and bloodstream. The olfactory epithelium makes up approximately 7% of the surface area of the nasal cavity and is connected to the olfactory bulb in the brain. Drugs and vaccines can be delivered to the brain past the blood-brain barrier through olfactory nerve cells. Compared to injectable vaccines, nasal vaccines can be advantageous because they are safe, painless, and easy to use, possibly allowing self-administration. Nasal vaccines do not require a needle, which eliminates pain from needlestick injuries and safety concerns due to cross-contamination and needle disposal. Some studies also show that intranasal vaccines can generate cross-reactive antibodies that could lead to cross-protection.
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