HUB's LIST of medical fun facts

“COVID vaccination world-wide prevented 19.8 million excess deaths.”
– Lancet Infectious Disease 2022

Vaccinations against infectious diseases have averted 154 MILLION world-wide deaths —  95% of those averted deaths were  children under 3 yeas old — during the fifty years from 1974 to 2024. Vaccinations against COVID, flu, and pneumococcus bacteria were NOT included in this study of prevented deaths.

Measles vaccination was the by far the winner in all regions and at all income levels at 94 million saved. Tetanus and Pertussis (whopping cough) were number two and three.  Not surprisingly the impact of vaccinations was the highest in low-income  and lower-to-middle-income countries. (Sci Am November 2024)

Measles vaccine is administered by injection. Low- and lower-income countries have less robust infra-structures. Vaccines in low income countries are often delivered by non-physician providers arriving at a village by bicycle. Vaccines are sometimes hard to store; need refrigeration, have expiration dates, etc. Syringes, needles, and alcohol swabs may be scarce. Needles hurt, or are perceived to be hurtful and/or dangerous. BUT the measles vaccine is an outstanding success world-wide.

Wouldn’t it be great to deliver vaccinations by a nasal spray. The FDA has just approved a nasal spray against the flu; available in the fall of 2025 for use at home via website order for ages 2 to 49 years old. (Children on aspirin, people with a history of asthma, people over 50, and  immunosuppressed people will not be eligible for its use.) Your COVID booster in 2027 might be a “spritz up your nose.”

All air-borne viruses (like measles, COVID, influenza) infect us by being breathed in. The first line of our protection is the mucosal cells in our nose. The nasal mucosa has immune cells that can produce blocking antibodies against viruses as well as killer cells to actually kill infected cells. This local immune response is faster and can be more potent then the response to injected vaccines, which have to travel by our blood stream to immunity cells in our lymph nodes to generate a response.

Researchers are particularly interested in this local nasal response to COVID because it may  block the spread of the COVID virus throughout the rest of the body, which might decrease the impact of “Long COVID”. The nasal flu vaccination does eventually activate the immune response of our lymph glands, so that the duration of immunity is the same as from injected vaccine.

The FluMist story illustrates some of the difficulties in developing nasal spray vaccines. FluMist was developed in 2003 and was used extensively and successfully by most pediatricians to prevent Influenza A and B   Unfortunately, it proved less successful in preventing the new strain of influenza (H1N1) in 2009, and it was not recommended as flu protection in subsequent years. According to the CDC, each year flu causes 41 million illnesses, 710 thousand hospitalizations, and 51 thousand deaths in the U.S. so effective vaccination against the flu is really important. FluMist has since been reformulated, and is now effective against Influenza A, B, and H1N1. It may be available to eligible people in the fall of 2025.

So what’s the problem with nasal vaccinations?

1. It’s hard to measure the immune response of nasal mucosa cells. Injectable vaccines result in antibodies that can be measured in a blood sample. There is no blood test for the cellular immune response of the nasal cells.
2. Nasal hair and microscopic cilia can physically block vaccine droplets from actually contacting the mucosal cells.
3. Nasal cells can develop “immunological tolerance”. Millions of foreign proteins are breathed in through our nose, most of them harmless, and the nasal cells can grow more tolerant in their decisions as to which are harmful. And that can dampen the immune response. Young children have less exposure to previous flu strains, so nasal immune tolerance is not a problem for them, and some countries in Europe still use flu nasal spray vaccine for children.
4. Various adjuvants (special agents) have been used to overcome tolerance, but unfortunately some have caused undesirable side effects (the inside of the nose is very close to several facial nerves and the brain).
5. The nasal immune response may completely demolish a new strain of flu virus in the nose (as we know, the flu virus changes every year) , so that the lasting immunity for the new flu strain does not develop from the lymph gland cells because those lymph gland cells never “see” the new virus.

Vaccine developers are trying to skirt all these barriers for a nasal spray COVID vaccine. The proof of the pudding, of course, depends on how well the vaccines protect people from disease in large,  complicated, and lengthy clinical trials. One company used a bird respiratory pathogen virus (Newcastle disease virus, NDV) that is harmless in humans to carry COVID vaccine particles through the nose and into the lungs. A small, early clinical trial showed that its vaccine (CastleVax) was effective.  Results from a 10,000 person trial of this NDV nasal spray vaccine is expected in 2026.  FDA approval, of course, will depend on who the FDA chief is in 2026, and remember, “The past price of a stock does not predict future price.”

The success of the injectable COVID vaccines has set a high effectiveness standard for nasal spray vaccinations. Researches hope that nasal spray inoculations might prove to be easier and effective for COVID boosters. But, unless the CDC removes its ban on the use of unused COVID injectable vaccine by basic researchers (a 2020 regulation when the vaccine was scarce), the development of effective nasal vaccines may take longer than expected (also depends on who the 2026 CDC chief is).