Rahul Dhounchak, Assistant Professor,

Geeta Institute of Pharmacy,

Geeta University

Vaccines play a crucial role in preventing infectious diseases by stimulating the immune system to recognize and fight pathogens. They are available in various forms, primarily injectable and oral doses. Both types of vaccines are designed to induce immunity, but the way they are formulated, administered, and the immune responses they trigger can differ significantly.

1. Vaccine Types and Formulation

• Injectable Vaccines:
  • Composition: Injectable vaccines often contain inactivated (killed) viruses, live attenuated (weakened) viruses, or subunit vaccines (containing parts of the pathogen). Some may also contain adjuvants—substances that enhance the immune response.
  • Formulation: Typically, injectable vaccines are liquids or suspensions that can be delivered directly into the muscle or under the skin. These formulations are designed to stay stable in the body and stimulate immune cells at the site of injection.
• Oral Vaccines:
  • Composition: Oral vaccines are often made from live attenuated (weakened) viruses or bacteria, or from inactivated pathogens. For example, the oral polio vaccine (OPV) and the oral rotavirus vaccine contain live, weakened forms of the virus.
  • Formulation: Oral vaccines are usually administered in liquid form or as tablets, capsules, or powders. which plays a crucial role in fighting infections that enter the body through the mouth.

2. Mechanism of Action

• Injectable Vaccines:
  • Immune Activation: Injectable vaccines typically stimulate a immune response by delivering the vaccine components directly into the bloodstream or muscle. This allows the immune system, particularly T-cells and B-cells, to recognize and remember the pathogen. The immune response generated is systemic, meaning it protects the whole body.
  • Antibody Production: Injection generally induces strong production of antibodies and activates other immune pathways like cellular immunity, which can lead to long-lasting protection.
• Oral Vaccines:
  • Immune Activation: Oral vaccines trigger responses in the gut-associated lymphoid tissue (GALT), which includes mucosal immunity. The immune cells in the gastrointestinal tract (e.g., mucosal IgA antibodies) help prevent infections that enter through the mouth. This immune response is often localized but can also generate systemic immunity.
  • Mucosal Immunity: Oral vaccines are likely to stimulate mucosal immunity, which is essential for defending against pathogens that enter through mucous membranes, such as the intestines and respiratory tract.

3. Delivery and Administration

• Injectable Vaccines:
  • Delivery: Injectable vaccines are usually administered via intramuscular (IM), subcutaneous (SC), or intradermal (ID) routes, meaning they are injected directly into the body.
  • Administration Method: Requires healthcare professionals for injection. It can be more painful compared to oral administration, and it may require a needle, which some individuals are afraid of.
• Oral Vaccines:
  • Delivery: Oral vaccines are consumed either as liquids, tablets, or capsules. They do not require specialized medical professionals for administration, making them easier to distribute, especially in low-resource settings.
  • Convenience: Oral vaccines are more convenient, as they can be taken by individuals without the need for needles or injections.

4. Immune Response and Efficacy

• Injectable Vaccines:
  • Stronger Systemic Immunity: Injectable vaccines are typically more effective at stimulating a strong, long-lasting immune response, particularly in terms of antibodies in the blood.
  • Broader Protection: Since they stimulate a systemic immune response, injectable vaccines tend to provide more comprehensive protection, especially against severe forms of diseases like diphtheria, tetanus, and hepatitis.
• Oral Vaccines:
  • Localized Protection: Oral vaccines stimulate responses in mucosal surfaces, which helps to prevent infections at the point of entry (e.g., the intestines or respiratory tract).
  • Less Durable: Oral vaccines may not always provide as long-lasting immunity as injectable vaccines because the immune response is often more localized and may require boosters to maintain protection.

5. Stability and Storage

• Injectable Vaccines:
  • Storage Conditions: Injectable vaccines often require cold storage (refrigeration) to maintain stability. Some vaccines, especially live attenuated vaccines, are sensitive to temperature changes, which can affect their efficacy.
  • Shelf Life: Injectable vaccines generally have a defined shelf life, and their stability is more predictable when stored properly.
• Oral Vaccines:
  • Storage Conditions: Oral vaccines may also require refrigeration but can sometimes be more stable at higher temperatures, depending on the formulation.
  • Stability Challenges: Oral vaccines, particularly those based on live microorganism, may be sensitive to environmental factors like temperature and humidity, which could reduce their effectiveness over time.

6. Cost and Accessibility

• Injectable Vaccines:
  • Cost: Injectable vaccines can be more expensive to manufacture and distribute because they often require complex storage and handling, such as refrigeration.
  • Global Distribution: Distribution of injectable vaccines can be challenging in low-resource areas because of trained healthcare workers for administration.
• Oral Vaccines:
  • Cost: They are generally cheaper to produce and distribute, especially in terms of storage, as they do not require refrigeration as strictly as injectable vaccines.
  • Global Distribution: Oral vaccines are more accessible in areas with limited healthcare infrastructure because they are easier to administer and can be distributed without need for special storage or trained medical staff.

7. Examples

• Injectable Vaccines:
  • Examples:
    • Measles, Mumps, Rubella (MMR) vaccine
    • Hepatitis B vaccine
    • Diphtheria, Tetanus, Pertussis (DTP) vaccine
    • Influenza (flu) vaccine (injection form)
    • COVID-19 vaccines (e.g., Pfizer, Moderna)
• Oral Vaccines:
  • Examples:
    • Rotavirus Vaccine
    • Typhoid Vaccine (oral form)
    • Cholera Vaccine (oral form)

1. Understanding the Challenges

• Stomach Acidity: The stomach’s acidic environment (pH 1.5-3.5) can degrade proteins, including many vaccine antigens, making them ineffective.
• Digestive Enzymes: Enzymes in the stomach and intestines break down proteins and other vaccine components before they can be absorbed into the bloodstream or stimulate an immune response.

2. Methods for Converting Injectable Vaccines into Oral Form

Scientists use a combination of techniques to overcome the barriers that prevent oral vaccines from being as effective as injectable ones.

a. Protecting the Vaccine Antigen

• Encapsulation: Encapsulating the vaccine in protective coatings (such as microencapsulation or nanoparticle delivery systems) helps shield it from stomach acids and digestive enzymes. The protective coating ensures that the vaccine reaches the intestines intact, where it can then stimulate immune system.
  • Example: Encapsulating the vaccine antigen in biodegradable polymers or liposomes.
• Enteric Coating: The vaccine can be coated with a material that protects it through the acidic environment of the stomach but dissolves in the more neutral pH of the small intestine. This is a common strategy for making certain oral drugs, like certain probiotics or antibiotics, effective.

b. Stabilizing the Vaccine Antigen

• Thermostable Antigens: Some vaccines may need to be modified to withstand the harsh environment of the digestive system. This could involve genetic engineering or modifying the formulation to enhance the stability of the antigen.
  • Example: Genetic modification of proteins to make them more heat-stable and resistant to degradation.
• Adjuvants for Oral Vaccines: Adjuvants can be used to enhance the immune response of oral vaccines. They help activate the immune system even if the antigen is in a less-than-ideal form due to degradation in the digestive system. These adjuvants could be molecules that enhance the vaccine’s effectiveness when administered orally.
  • Example: Mucosal adjuvants like cholera toxin or other immunomodulators that stimulate the immune system in the gut.

3. Examples of Successful Oral Vaccines

There are already several successful oral vaccines, though they differ from injectable vaccines in how they are formulated. Some of these include:

• (OPV): The OPV uses a live attenuated polio virus. The virus is designed to survive in the digestive system, where it stimulates an immune response both locally (in the gut) and systemically.
• Oral Typhoid Vaccine: The Ty21a strain of Salmonella Typhi is used as an oral vaccine to protect against typhoid fever.
• Cholera Vaccine: There is also an oral cholera vaccine (e.g., Dukoral), which contains killed bacteria and is taken in liquid form.

4. Challenges in Converting Injectable Vaccines to Oral

• Antigen Stability: The stability of the vaccine antigen during passage through the digestive system is a major challenge. Injectable vaccines often rely on the preservation of specific protein structures that might be altered or degraded during digestion.
• Immune Response: Injectable vaccines typically produce strong systemic immunity, while oral vaccines primarily induce mucosal immunity. Changing the immune response type (from systemic to mucosal) may require altering the vaccine’s formulation and understanding how the immune system reacts to oral antigens.
• Regulatory and Safety Concerns: Oral vaccines need to be carefully tested for safety and efficacy, especially for diseases where vaccines have not previously been available in oral form. Regulatory bodies like the World Health Organization (WHO) or the FDA require rigorous testing of vaccines before they can be approved for widespread use.

5. Future Directions

• Nanotechnology: The use of nanomaterials and nanotechnology for vaccine delivery could offer innovative ways to create oral vaccines. Nanoparticles can protect antigens and deliver them to the correct part of the intestine to elicit a strong immune response.
• Genetically Engineered Bacteria: Advances in genetic engineering could enable the development of bacteria designed to deliver vaccine antigens directly to the mucosal immune system in the intestines.
• Oral mRNA Vaccines: The success of mRNA vaccines, like those used for COVID-19, has sparked interest in developing oral mRNA vaccines. If researchers can find ways to protect mRNA from degradation in the digestive tract, oral mRNA vaccines could become a reality.

Oral vaccines can be a convenient alternative to injections, but there are several reasons why they are not always used instead of injectable vaccines:

1. Immune Response Differences: The immune responds differently to vaccines administered through the mouth compared to those given by injection. Injectable vaccines usually trigger a stronger immune response, especially in terms of generating long-term immunity, because they are often delivered directly into the bloodstream or muscle tissue, where immune cells can more quickly recognize and respond to the pathogen.
2. Digestive System Breakdown: When a vaccine is taken orally, where stomach acids and enzymes can break down the components of the vaccine, potentially making it less effective. This is especially a concern for protein-based vaccines, as they might be degraded before they can stimulate an immune response.
3. Stability Issues: Some vaccines require specific conditions to remain stable, and it can be challenging to ensure that oral vaccines maintain their potency through the digestive tract. Injections can be more stable because they are usually in liquid form, which can be stored more easily.
4. Targeted Delivery: Injectable vaccines can be precisely delivered to areas where they are most effective, such as muscles or tissues that are rich in immune cells. Oral vaccines may not reach the same cells in the body, making it harder to elicit immune response.
5. Need for Adjuvants: Oral vaccines may require special additives called adjuvants to help enhance the immune response. These are sometimes necessary to ensure that the immune system recognizes the vaccine properly. Injections, on the other hand, often don’t need as many adjuvants because the immune system directly encounters the vaccine in a more controlled manner.
6. Examples and Research: While oral vaccines exist (like the oral polio vaccine), they tend to be used for specific diseases where they are effective in triggering an immune response through the gut. However, for many diseases, injectable vaccines remain the preferred method for ensuring a strong and reliable immune response.

In short, the decision to use oral or injectable vaccines depends on factors like the disease being targeted, the nature of the vaccine. Oral vaccines are great for certain diseases, but injectable vaccines are more commonly used because they are more reliable in inducing a strong and lasting immunity.

Conclusion

Both injectable and oral vaccines have their advantages and limitations, depending on the target disease, the immune response needed, and logistical considerations. Injectable vaccines are often preferred for systemic, long-lasting immunity, especially against diseases that require strong, sustained protection. Oral vaccines, on the other hand, are easier to administer, more accessible, and often provide effective protection for diseases that primarily affect the mucosal surfaces.

The choice betweenl vaccines depends on various factors, including the nature of the disease, the required immune response, and global health needs. As vaccine research continues, innovations in both types of vaccines may lead to more effective, accessible, and stable immunization options for preventing a wide range of infectious diseases.

Transforming an injectable vaccine into an oral vaccine involves overcoming several scientific and technical challenges. The process requires ensuring that the active components of the vaccine remain effective when taken through the digestive system. Oral vaccines stimulate mucosal immunity, whereas injectable vaccines generally provoke systemic immunity.