How vaccines are developed

The process

Step 1: The concept

Scientists begin by studying how a disease works. For example, how a virus infects the body and which parts of it are most important for triggering immunity. From there, they design a vaccine that will ‘teach’ the immune system to recognise and fight the disease.

• Whole-microbe approach: these vaccines use the whole germ, or pathogen (virus or bacterium), but in a form that does not cause illness. There are two main types.
  • Inactivated vaccines: the pathogen is killed or inactivated using heat, chemicals or radiation. Influenza (flu) and polio vaccines are made this way.
  • Live-attenuated vaccines: the pathogen is still alive but weakened so it cannot cause disease in healthy people. Examples are measles, mumps and rubella (MMR), chickenpox and shingles vaccines. These vaccines usually provide strong protection against the disease but are not recommended for people with weakened immune systems.
• Subunit, recombinant, polysaccharide and conjugate approach: these vaccines use only specific components of the pathogen, such as proteins, sugars or capsid (the casing around the pathogen), that the immune system recognises. Examples include Hib (haemophilus influenzae type b), hepatitis B, human papillomavirus (HPV), whooping cough (part of the DTaP combined vaccine), pneumococcal, meningococcal and shingles vaccines.
• Toxoid approach: these vaccines use the toxin (the harmful product) made by the pathogen that causes the disease to stimulate immunity. The body’s immune system responds to the toxin directly instead of the pathogen itself. Examples of toxoid vaccines include diphtheria and tetanus vaccines.
• Viral vector approach: these vaccines use a harmless, modified virus (the vector) to deliver genetic instructions into the body’s cells, which then produce a protein of the pathogen that the body’s immune system can respond to. This method was used in the Ebola vaccine and in some COVID-19 vaccines, such as the AstraZeneca vaccine.
• mRNA/DNA approach: these vaccines provide the body with genetic material (messenger RNA [mRNA] or DNA) that instructs cells to make a protein from the pathogen. The immune system recognises this protein as foreign and responds. mRNA technology was used in developing COVID-19 vaccines.
   

Step 2: Pre-clinical trials

Before a vaccine is trialled in people, researchers assess it for many years using pre-clinical studies. The aim of these studies is to decide whether the vaccine can generate an immune response, and whether it is safe enough to try in people. There are two types of pre-clinical trials.

• Laboratory research: Researchers test how a vaccine interacts with cells and whether it produces an immune response.
• Animal studies: Sometimes vaccines are tested in animals to see how the vaccine behaves in a whole body and to look for safety issues.
   

Step 3: Clinical trials

When a vaccine passes the pre-clinical trials, it is then tested in humans in three carefully controlled steps.

• Phase 1: The vaccine is given to a small group of healthy volunteers (usually of fewer than 100) to test initial safety and side effects, confirm an immune response and establish the correct dose.
• Phase 2: The vaccine is given to hundreds of volunteers to explore how strong the immune response is at different doses and to continue monitoring safety.
• Phase 3: The vaccine is given to thousands or tens of thousands of people to test how well the vaccine prevents a disease in a large population.
  
  To do so, the clinical trial compares the immune response of people in a vaccinated group with that of people in a group who didn’t receive the active vaccine. This group may have received a vaccination with no active ingredient (a placebo) or another approved vaccine that is used to treat different disease (control group). Common and rare side effects are monitored over many months during this phase.

Find out more about phases of clinical trials.
 

Approving the vaccine for use

If the vaccine is proven to be safe and effective in clinical trials, regulatory authorities of different countries around the world assess it to make sure it meets strict standards for quality, safety and effectiveness. In Australia, this role is carried out by the Therapeutic Goods Administration (TGA), Australia’s national regulatory agency.

Once approved at the national level, manufacturers may also apply for prequalification from the World Health Organization (WHO), which ensures vaccines meet international standards, particularly for countries that may not have their own stringent regulatory agency. During global health emergencies such as pandemics, the WHO Emergency Use Listing Procedure can be used to speed up access to vaccines while maintaining strict safety checks. 
 

Manufacturing the vaccine

The manufacturing process for vaccines is complex and very tightly regulated as it involves working with biological materials that require careful handling. The steps can vary depending on whether the vaccine is inactivated, live attenuated, subunit or mRNA. 

• Production: Vaccines are made in highly specialised facilities that meet strict biosafety and quality standards. Manufacturers must ensure they can produce the number of vaccine doses they agreed to provide to the government without compromising quality.
• Vaccine packaging: After vaccines are produced in bulk, they are divided into safe, usable doses and packaged in glass vials, pre-filled syringes or ampoules. The packaging must protect the vaccine during cold storage and transport, which often occurs across long distances and in challenging conditions.
• Quality control: Every batch of vaccine is tested for safety, purity and potency at various stages of production before it is distributed.
• Distribution: Temperatures are strictly controlled and monitored during transport and storage to make sure vaccines remain effective. Most vaccines are kept at refrigerated temperatures between 2°C and 8°C. Others, including some childhood vaccines, may require freezing at around −20°C.  
   

Vaccine safety monitoring after approval

Once a vaccine is approved and in use, it continues to be carefully monitored and evaluated. This includes monitoring to detect any potential very rare or long-term side effects that might not have appeared during clinical trials. In Australia, the TGA is responsible for monitoring the safety of vaccines after they are supplied.