*Thread* Have had friends and family ask about the intranasal or oral COVID vaccines currently in development (vaccine in pill or spray form!). Here’s an overview🧵
All COVID vaccines currently authorized for use are delivered by injection. While these are highly effective, mucosal delivery of vaccines would be ideal due to:
- Ease for self-administration (easy to take a pill or sniff a spray)—do not need to be administered by a medical
professional and can be sent directly to people’s homes or hard-to-reach areas where individuals can be given the vaccine to take themselves.
- Ease of distribution compared to injection-based therapies
- May not need refrigeration making it easier to ship and store
BONUS: added benefit for the 1 in 10 who have needle anxiety and needle-free administration would also eliminate needle-stick injuries, which occur accidentally in approximately 5% of health-care workers each year (@heysciencesam)
Quick definition:when we say mucosa we mean moist, inner lining of some organs and body cavities (such as the nose, mouth, lungs, and stomach)- think anything covered in mucus. Nasal (and oral) mucosal surfaces are the primary portal of entry for pathogens like SARS-CoV-2,
so mucosal vaccination can be effective for induction of long-lasting systemic/mucosal immunity by interrupting transmission of the virus at earliest stage (maybe even stopping infection at all with sterilizing immunity).Mucosal membranes are packed with immune cells and proteins
Injectable vaccines (Moderna / Pfizer/ J+J / AstraZeneca) are highly effective and able to induce protective responses that include circulating antibodies, a portion of which do get eventually transported into the nasal mucosa, however are generally poorer inducers of immunity
at the mucosal surface. For maximal protection we want virus to encounter secretory IgA in the mucosa on entry (it’s the most abundant type of antibody there), + then once/if it reaches the terminal airways and alveoli it enters environment dominated by IgG from the circulation.
This is what scientists are hoping to achieve by developing mucosal vaccines (such as oral or intranasal vaccines). Although oral / nasal delivery may be most desirable and patient-accepted route of administration (and more cost-effective!),there are few major obstacles to note:
1/ The mucosa and their mucus-secreting layers are really difficult barriers to infiltrate (their main job is to protect the body from the invasion of pathogens e.g through the gut!). For an oral vaccine to work it has to be delivered to the intestine, transported across
the mucosal barrier for antigen-presenting cells to “see” it and to activate memory immune responses- but that’s hard to do when you have to pass through a thick layer of mucus, harsh gastric acid, and hydrolytic enzymes that break down any antigens they come into contact with.
2/This means that higher doses of antigen are needed to activate the right immune responses when compared to injectable vaccines. However dose can’t be too high as this runs the risk of activating wrong immune responses and the body may recognize it as non-pathogenic and
avoid triggering an immune response, resulting in immune tolerance instead of protection.

3/ Often to be effective, mucosal vaccines have to be live-attenuated vaccines (they contain living but weakened form of the pathogen),
meaning they cant be given safely to severely immunocompromised patients.

4/ It’s also harder to assess mucosal immunity- nowhere near as simple as getting a blood draw to check for circulating antibodies.
Thanks to @ENirenberg for adding to this thread!

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