Inject muscle like deltoid and thigh or Stick a Needle in my Eye?
Where our immune system is trained matters for long-term memory generation. Where we place foreign material for teaching the immune system to understand dangerous pathogens can be important on outcome measures. Vaccination campaigns have only recently switched to injecting myofibrils (muscle cells) in the early 20th century (1920s-1940s) away from the more immunogenic skin targets of earlier vaccination campaigns.
I believe the smallpox vaccination campaign was successful at reducing morbidity and mortality of smallpox disease. Edward Jenner injected only skin deep in 1796. The Langerhans cell is an immune presenting cell found in the skin in 1869 among the many layers of skin immunity. Other immune skin cell residents make the skin an ideal target for educating your immune system. The skin already is engaged in protecting you from the pathogens of the outside world, but your muscles are tucked deeper inwards and are more engaged with the function of locomotion. Muscles can generate immunity as demonstrated by antibody formation after injecting them, but they are not the best immune organs because they are not designed to protect you like your skin from the outside world.
Muscles are great targets for injection when you want dispersion of the molecule to the whole body to interfere with receptors as an example. This is where the molecule is a lock in key fit. When you want to teach the immune system to learn from exposure or you want to vaccinate, you want exposure controlled and slowly released over time. You don’t want rapid absorption throughout the body with infectious disease vaccines as side effects are more likely with rapid absorption.
There are articles and studies supporting mucosal applied vaccines (sublingual, oral, conjunctival (eye drop)). The same human papilloma subunit particles injected into deltoid muscle have been studied as an eye drop. That is again because the layers of immunity are structured to understand from an “outside in” exposure. When a needle is plunged past the outer layers into muscle fibers you get a different type of immunity as you bypass the outside “skin cell” guardians. You also get faster absorption into the body with intramuscular injections. In my opinion, faster absorption may lead to increased side effects like myalgias (muscle aches), fevers, and blood vessel and neurologic inflammation.
The FDA did approve intradermal flu vaccines in 2014 in the USA. Fluzone Intradermal was the same “stuff” used in the intramuscular vaccine used for decades but dose-reduced to only 0.1 ml, down from the 0.5 ml intramuscular dose. The only reason it was withdrawn was due to cultural/political issues of a slightly more difficult administration technique to hit the layers of the immune skin. We just witnessed an intradermal vaccine campaign in August 2022 with the new Mpox outbreak. A reduced intradermal dose of 0.1 ml was used to vaccinate 5x the people compared to using 0.5 ml in the muscles. It is the same way Edward Jenner did it centuries ago. It was considered a successful campaign.
As an editorial statement, it is our belief that the intradermal route represents an opportunity for better immunity. It has been studied in small numbers in the allergy literature, as we know delivering allergens to different immune “compartments” like sublingual, oral, subcutaneous, intradermal, and even intralymphatic (directly into the lymph nodes) can be very effective.
My research tells me that there are less systemic side effects but slightly more local side effects with vaccinating the skin as opposed to the muscles. We must remember that our immune system can over-react to any exposure delivered to any body system at any time. We do have some science on underlying conditions that help make vaccination campaigns safer and more successful (see vaccine handout recommendations).
In 2021, I had never witnessed so much politicization of vaccine science. Vaccines will always have controversy as they are not completely risk free. We need more open debate/discussion and better post-marketing surveillance of safety and efficacy. We should try and find the most effective dose and route again as Edward Jenner did some 225 years ago. Most physicians and pharmacists do not have enough training in vaccine science. They simply rely on our public health authorities since there is so much information in medicine today. Vaccine science is contaminated with several biases. Headlines you see about vaccine studies may suffer from multiple biases. For example, I can find articles that state vaccine recipients have less dementia. While it may be possible, I can see the “selection and life-style bias” in these studies because they are not prospectively randomized. They are retrospective. The reason for the lower dementia may not be because of receiving vaccines but may be from other underlying health conscientious factors like diet, exercise, and socio-economic power. It is likely that these factors are protecting against dementia. It is a difficult study to conduct prospectively, however.
Unfortunately, you cannot easily receive vaccines by intradermal routes. Most pharmacies follow the package insert for intramuscular administration of flu, covid, rsv, shingles, hpv, and pneumonia as a convention. Your voice can ask for better science for safety and efficacy.
DJFMD opined 12-2024