Vaccination delivery through a pill.

Vaccinations have become incredibly important due to COVID-19 and the vaccine rollout needs to be faster and more efficient in order to achieve global herd immunity. Vaccines, the COVID-19 vaccine being an example, are usually injections that contain dead or weakened versions of the pathogen. However, there a numerous disadvantages to these traditional vaccines:

  1. They need to be kept refrigerated from production to the time of injection. This increases the cost and complicates the delivery process. This also means that hotter countries will be less likely to have a sufficient vaccine program due to the undesirable climate.
  2. Sterile needles need to be used. Sterile needles are used to prevent infection after injection because the blood vessels have been exposed. In developing countries, it can be more difficult to safely administer vaccines due to lack of proper hygiene.
  3. They need to be administered by a trained healthcare professional. Vaccines are injections that can not be self administered. This means that vaccines are not reaching communities without proper public health systems. For example, the rate of vaccine rollout in rural areas will be slower than cities where access to health care professionals is higher. In contrast, oral vaccines can be self administered and do not require specialists.
  4. People are less likely to trust an injection when compared to a pill. Taking a vaccine pill is far less invasive.

Overall vaccines are expensive and production is limited to developed countries. As we have seen with COVID-19, the vaccine rollout in non-Western countries has been limited which threatens the global goal of herd immunity.

Instead of the traditional vaccine, scientists are developing a vaccine in the form of a pill. This oral vaccine provides some benefits in terms of being cost effective and more efficient for widespread administration, which makes it a desirable alternative. However, there are many challenges scientists face when creating this vaccine. The oral vaccine enters through the gastrointestinal tract and a series of steps is required to ensure a successful immunisation:

1. Successful delivery and an active antigen attached to the intestine

2. Transport across the mucosal barrier

3. Activation of the immune cells (APC’s, T cells, B cells)

The main challenge is the successful delivery because the human digestive system has evolved to get rid of any pathogens ingested. The defence systems would break down the pathogen before the antigens reach the immune system for detection and to trigger an immune response. The first barrier is the saliva which contains digestive enzymes. These enzymes catalyse the breakdown of pathogen cell walls. Next is the stomach acid which has a high concentration of hydrogen ions, creating a pH that is too low for pathogens to survive in. They would also be broken down by proteolytic enzymes that degrade the proteins that are responsible for antigen structure. Lastly, the bile in the small intestine interferes with the pathogen before it reaches the absorption stage where the immune cells would recognise the pathogen.

Despite these challenges, scientists are beginning to develop new ways to administer oral vaccinations. Bacteria are currently under research.

To protect a pathogen against the saliva, dried bacteria are used which will prevent the activation of enzymes. The pills would also be coated to protect against the acid in the stomach. The coating would eventually dissolve to release the pathogen. The significant problem is the bile. The dried bacteria (that were dried to prevent degradation by the saliva) loose their tolerance for bile. Instead the bacteria are rehydrated before the bile reaches it by using Bile-acid Absorbing Resins (BARS). BARS slow down the movement of bile so that water moves faster than it. Therefore, the bacteria are rehydrated with water before the bile gets to it to destroy it. The capsule that is used to deliver the bacteria is broken down to release the bacteria. The bacteria then stick to the lining of the small intestine so that the immune cells can recognise them.

This gastrointestinal route for the vaccine creates some challenges. However, the lining of the small intestine also contains many immune cells which creates a stronger immune response, thus making the vaccine effective. The immune response induces mucosal immunity which protects more effectively against mucosal infections at mucosal surfaces. Below you can see that the immune cells lie near the lymph node (where lymphocytes are matured) and in the lining of the small intestine.

Photo Credit:

Oral vaccinations could help to increase the scope of vaccination programs and could help tackle the current COVID-19 pandemic. However, many challenges are still faced which has limited scientists. Despite this there are some oral vaccines such as the oral polio vaccine!

Photo Credit: UNICEF

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