All About Different Vaccine Delivery Methods

A shot? A spray? Drops in the mouth? There are multiple ways to receive a vaccine. Find out the factors that determine how certain vaccines are administered and why.

1. How are vaccines given? 

Vaccines are administered in a variety of ways depending on the type of vaccine, the target disease, and the desired immune response. The most common methods are:  

• Intramuscular injection – a shot delivered into the quadricep muscle in the thigh or the deltoid muscle in the arm  

• Subcutaneous injection – a shot delivered in the fatty tissue under the skin of the thigh, belly, or upper arm 

• Orally – drops or a pill taken by mouth 

• Intranasally – a spray or mist in the nostril  

• Jet injection – a high-pressure stream of fluid delivers vaccines into the skin without a needle 

2. What factors determine the way a vaccine is delivered?

Different vaccine delivery methods are often dependent on the vaccine being given, the desired immune response, ease and safety of administration, and target population.  

• Intramuscular injections are currently considered the optimum delivery method for most vaccines because they are absorbed quickly into the bloodstream and optimize the effectiveness of the vaccine’s ability to trigger an immune response. There is also less of a chance of an adverse reaction at the site on the body where the vaccine was given. Intramuscular injections are performed with a syringe needle, a process that requires more training to administer than some other methods, which makes them a bit less desirable for use in mass vaccination efforts compared to oral or intranasal vaccines. Yet, despite the necessary staff training and potential for hesitancy due to fear of needles especially for children, intramuscular injections have been extremely successful for mass vaccination campaigns, as seen during the COVID-19 pandemic. Examples of intramuscular vaccines include tetanus, diphtheria, and COVID-19. Sabin’s investigational vaccines for Marburg and Sudan ebolavirus are both intramuscular injections

• Subcutaneous injections take longer for the body to absorb, and the vaccine is released at a constant rate. This makes them more effective for live attenuated vaccines (weakened form of viruses) and certain inactivated vaccines. Subcutaneous injections also offer flexibility in the anatomical site of administration and are often used in animal models in the upstream phases of vaccine development. Examples of subcutaneous vaccines include MMR (mumps, measles, rubella), yellow fever, varicella, and meningococcal polysaccharide.

• Oral vaccines are absorbed via the gastrointestinal tract which makes them highly effective at building immunity for diseases that affect the gut, such as polio, cholera, and rotavirus but less so for vaccines that require a strong systemic immune response. Oral vaccines can be administered quickly and don’t require special training.  

• Intranasal sprays trigger mucosal immunity, which is beneficial for respiratory pathogens like influenza, but have similar limitations to oral vaccines in that they are not always effective at triggering a systemic immune response. Intranasal doses can be self-administered. 

Infants, children, and needle-phobic adults have different needs regarding vaccine delivery methods. For example, the oral polio vaccine is easy to give to infants, but an intranasal flu vaccine is more suitable for healthy children and adults.  

3. Are there any new technologies for delivering vaccines on the horizon? 

There are several new advancements in vaccine delivery methods that aim to enhance efficacy, accessibility, and patient compliance. Of particular importance is reducing or eliminating the need for cold-chain transport and storage, which comes at a significant cost particularly for low- and middle-income countries. Notable developments in vaccine delivery technology include: 

• Microneedle Patches (MPs) are transdermal patches with tiny needles that painlessly penetrate the skin’s outer layer to deliver vaccines. These patches can be self-administered, eliminating the need for trained health care professionals. They also offer logistical advantages, such as reduced reliance on cold chain storage. A recent trial demonstrated that MPs are as effective as traditional injections for measles and rubella, with over 90% of infants protected from measles and 100% from rubella after one dose. Superior cellular immunity has been noted for MPs due to the type of T cells activated in the skin. 
• High-Density Microarray Patches (HD-MAPs) are small skin patches with microscopic prongs that deliver the vaccine to immune cells just beneath the skin surface. Compared with conventional MPs, HD-MAPs have a higher density of microneedles resulting in better delivery to immune cells and potentially stronger immune responses. The improved delivery also means that, compared to more traditional approached such as intramuscular injections, less vaccine material can be used. This technology is currently undergoing clinical trials for bird flu vaccines and has shown promise in delivering multiple vaccines simultaneously without the need for refrigeration.  

<sub>1. Source: NIH and CDC
2. Source: NIH
3. Source: The Lancet and NIH</sub>