Nasal vaccines offer an option to those afraid of needles, situations where mass vaccination is required, or for those seeking an at-home option, but there are restrictions on who should receive the vaccination. Very young patients, patients aged 50 years or older, and some living with chronic conditions are not recommended to receive the nasal vaccine. Whatever the vaccine route, physicians considered the additional options a public health win as flu vaccines are recommended to avoid significant illness and hospitalization.

Injectable and nasal vaccines create different responses in the body, potentially making one more suitable for a respective patient group, according to experts. Injected influenza vaccinations offer a systemic response between about 30%-60% depending on the flu season and can take up to 2 weeks to reach full effectiveness, potentially leaving some patients vulnerable in that time, said experts.

Nasal vaccines prompt antibodies locally in the nasal and upper airway mucosa — where respiratory viruses enter the body. Following a reformulation and FDA approval for home use in 2024, the nasal option is among the recommended flu vaccines. However, according to 2022 CDC data, low uptake in the US has hindered data collection on comparable effectiveness domestically, though the nasal vaccination has been considered to be comparable to an inactivated, egg-based flu vaccine for children in other countries.

Currently, one intranasal vaccination is available in the US — FluMist, a live-attenuated influenza inoculation, which creates a response in the mucosal tissues.

“The bottom line is that the vaccines will prevent infection and severe disease when taken appropriately,” said Philip Robinson, MD, medical director of Infection Prevention and Hospital Epidemiology at Hoag, a nonprofit regional healthcare delivery network based in Orange County, California. “Nasal vaccines are as effective as subcutaneous vaccines, but there are some differences in the type of immune responses and immune system training between the two.”

General Considerations Based on Health and Age

As a baseline approach, nasal vaccination is safe and intended for healthy individuals between the ages of 2 years and 49 years, according to Robinson. “But it should not be given to patients who are pregnant, immunosuppressed, or those with chronic conditions like lung disease and diabetes,” he said.

Young patients who live with asthma or a recent wheezing profile have an increased risk for hospitalization and are not good candidates for nasal vaccination, according to Derek Corpus, MD, MBBS, a pediatric pulmonologist at Guerin Children’s Cedars-Sinai Children’s Health Sciences University, Los Angeles.

While current guidelines from the CDC advise exercising caution when administering to older children with asthma due to potential wheezing exacerbations, Corpus said he has seen encouraging results in this cohort. “For kids ages 2 years and up, the asthma safety profile is actually pretty great,” he said. “It’s well-tolerated, even in kids with a wheeze.”

Children aged 6 months to 2 years should receive a vaccine through injection. Children aged 2 through 8 years who are eligible for the nasal immunization require two doses (at least 4 weeks apart) if it’s their first time receiving the nasal vaccination. Injections also require two doses in the same age group.

Additional restrictions noted by the CDC for nasal vaccination are:

• An allergic reaction after a previous dose of influenza vaccine or having any severe, life-threatening allergies
• Children or adolescents aged 2 through 17 years currently taking aspirin or aspirin- or salicylate-containing products
• Received an influenza antiviral medication within the previous 3 weeks
• People currently caring for severely immunocompromised people who require a protected environment

For those living with a severely immunocompromised patient, the nasal vaccine can be considered if there’s an opportunity to limit contact with the individual for 7 days, explained Robinson. “This is important because, although rare, the immunocompromised patient could become infected with the live vaccine virus,” he said.

Those ineligible for flu vaccine injection according the CDC include:

• Infants younger than 6 months
• Anyone with a severe, life-threatening allergy to a previous flu shot or any vaccine ingredient
• Anyone experiencing a high fever or severe illness at the time of vaccination

There are also specific precautions for those currently taking aspirin or salicylates, as well as those living with certain health conditions, such as Guillain-Barré Syndrome.

Older individuals might remain at risk for contracting the flu after injection due to delayed circulation of antibodies, explained Eleonora Fedonenko, MD, an internal medicine physician with a private practice in Los Angeles. “It is slow to have mucosal sites that are effectively covered by these antibodies; therefore, there is a period of vulnerability to infection,” said Fedonenko. “This is particularly in older adults who exhibit considerable amounts of antibodies in serum whenever influenza vaccinations are administered but get the flu due to the fact that they did not have a ready mechanism of protection in their nasal tracts.”

When Engagement Combines With Efficacy

A nasal spray has become an attractive pain-free option for the pediatric population, said Corpus.“That’s probably the biggest benefit of utilizing intranasal,” he said. “It’s not a poke. And there are also probably adults who would much prefer not to have a needle that can cause some pain. People can get very apprehensive about using something that’s going to hurt them. This spray is much more perceived to be benign and less painful. The hope overall is that when people are deterred for any reason about receiving the syringe, whether it be an adult or a child, you can administer this as a less-burdensome option. Getting over that barrier is a huge win.”

Angela DeRosa, PhD, a clinical advisor at The Freedom Center, a network of addiction treatment centers based in Maryland, also suggested nasal inoculation for facilities that are conducting vaccinations in large-group settings. “Nasal vaccines are great at preventing infection of respiratory viruses or those that enter our system after being inhaled,” said DeRosa. “They are a great alternative as needle-free vaccinations for those who fear needles and in settings of mass vaccination.” While the use of nasal vaccines currently accounts for a reportedly much smaller percentage of overall flu vaccinations, its use is expected to increase with the approval of self-administration at home as well as caregiver-administration by the FDA.

Seasonal Unpredictability Among Adults and Pediatrics

Corpus also pointed out that aside from route of vaccination, the effectiveness of a particular vaccine in an individual flu season will vary. “There’s a lot of variability with subtypes and season from the viral standpoint,” he said. “One example is that the nasal vaccine didn’t do as well with a specific AH1N1 strain. But even then, the intranasal still does reduce the burden of upper respiratory tract infections.”

From season to season, providers might find that one method seems to be achieving better overall results than another method among people of all ages. “And those types of nuances are really difficult to determine for specific cases,” said Corpus. Overall, he said he has observed what appears to be better performance efficacy of nasal vaccines with the passing of time. “I think this has been apparent just by the nature of [companies] trying to get better products out,” he said. “The challenge is that with seasonality and mutations, effectiveness will always fluctuate to some degree. You can’t predict how the microbes or the viruses will mutate. That always gives a variable.”

There is also the potential of administration error with the nasal vaccine that could affect efficacy.

The Future of Intranasal Vaccination

Additional nasal vaccines are currently in development, including respiratory syncytial virus, COVID, and pertussis.Research into a potential vaccine to protect against Pseudomonas aeruginosa (PA) is also currently being conducted at New York Medical College (NYMC), where Paul Arnaboldi, PhD, has been awarded a grant by the National Institutes of Health totaling more than $500,000 to support efforts against the spread of the multi-antibiotic resistant organism, particularly among high-risk populations like long-term care facility residents, surgical patients, those prescribed immunosuppressive therapies, transplant patients, the older adults, those who have experienced burn wounds, and those living with cystic fibrosis.

“The spread of multi-antibiotic-resistant PA has made infections with this opportunistic pathogen increasingly difficult to treat,” said Arnaboldi, associate professor of pathology, microbiology, and immunology at NYMC. “There’s a big push for trying to find alternative methods to prevent or treat diseases. At the same time, PA is causing a lot of different kinds of systemic diseases, surgical-site infections, and other complications.”

Currently 6 months into the first year of the 2-year grant, Arnaboldi, in conjunction with Alison McCormick, PhD, at Touro University California, Vallejo, California, is using the tobacco mosaic virus (TMV) as a delivery platform to developing an intranasal protein subunit. TMV is a plant pathogen that does not infect animal cells and is highly immunogenic, being an optimal size and composition for recognition by the immune system. The modified version of the TMV has an extra lysine on its surface, making it possible to attach vaccine antigens directly to the virus, according to Arnaboldi.

Early tests are reportedly showing positive results, as the modified TMV was used to deliver PcrV — a protein found at the tip of the PA type III secretion system — along with an adjuvant called curdlan, which encourages an immune response. The researchers will now work to define additional vaccine antigens to create a multi-valent vaccine in an attempt to provide broad protection against multiple strains of PA and additional pathways that can be targeted to improve vaccine efficacy.

“What we’ve found over the years is that, when you inject a vaccine subcutaneously or intramuscularly, you get a very good immune response in the blood, but you don’t get a complete immune response on the mucosal surface,” said Arnaboldi. “However, in experimental settings, we’ve seen that when you vaccinate at a mucosal surface, you also get a good response in the blood. So the prevailing theory is that you could vaccinate mucosally or immunize mucosally and protect both areas.”

Robinson, Corpus, and DeRosa reported having no relevant financial disclosures.