Australia’s trusted immunisation experts
03 November 2023
| NewsThe Vaccination Insights project – national surveillance of drivers of under-vaccination in Australian children aged under 5 yearsRead the full article
A vaccine must go through several phases of clinical trials before it can be licensed. Before a vaccine enters clinical trials, it undergoes pre-clinical assessment, where the target antigen is identified, and the vaccine safety and efficacy are tested in laboratory and animal models.
In phase I clinical trials, typically dozens of participants are recruited. In this phase, the vaccine dose level and safety are tested. It takes at least 1 year for a phase I clinical trial to be complete. Not all vaccine candidates that complete phase I clinical trials enter phase II clinical trials.
In phase II clinical trials, hundreds of participants are recruited. In this phase, the immunogenicity and safety of the vaccine are tested. It is important to ensure that the candidate vaccine stimulates both humoral and cellular antibody responses against the target antigen. Very few candidate vaccines will have satisfactory phase II clinical trial results and move on to phase III clinical trials.
In phase III clinical trials, thousands of participants are recruited. In this phase, the safety and efficacy of the vaccine are tested. The virus must be circulating during the trial to determine if the vaccine is effective to protect against the virus or disease. Phase III trials take a few years to complete.
After collecting data, regulatory bodies assess vaccine safety and effectiveness before the vaccine is licensed. The whole process of vaccine development to licensure takes around 10 years (refer to Figure 1).
Figure 1: Conventional pathway of vaccine development
In the COVID-19 pandemic, the vaccine development pathway was accelerated. First, as SARS-CoV-2 is a coronavirus, it shares similarities with SARS-CoV-1 (Severe Acute Respiratory Syndrome, SARS) and MERS-CoV (Middle East Respiratory Syndrome, MERS). Prior work on SARS and MERS vaccines reduced time spent on pre-clinical assessment of COVID-19, and the target antigen was identified quickly.
Two months after the SARS-CoV-2 genome was sequenced and shared, the first phase I clinical trials began in March 2020. Phase II clinical trials began before phase I clinical trials ended. For many COVID-19 vaccine clinical trials, phase I and phase II clinical trials were combined to help speed up the progress. However, scientific design was not compromised as the dosage, safety and immunogenicity measures were evaluated. Phase III clinical trials also began before phase II clinical trials were complete. There were a few trials where phase II and phase III were combined.
Overlapping and combined phases of clinical trials, the urgency of a need for a safe and effective vaccine, international collaborative efforts, funding and pre-planning in manufacturing have allowed vaccine development time-frame to be compressed to about 10 months. COVID-19 vaccines are being rolled out for emergency use authorisation in several countries. However, as there are limited safety data, full registration of the vaccine will only be given after extended safety monitoring, which will take several years (refer to Figure 2).
Figure 2: COVID-19 vaccine development at pandemic speed