Pre-clinical research: years before any human is vaccinated

Long before a vaccine candidate enters a clinical trial, researchers spend months to years studying it in the laboratory and in animal models. They assess whether it produces an immune response, what dose range appears safe, whether it has toxic effects on organs, and how it should be stored and formulated. The vast majority of vaccine candidates never progress beyond this stage. Pre-clinical testing provides the first safety and feasibility evidence required before regulators will allow human trials to begin.

Phase 1: first-in-human safety testing

Phase 1 trials enrol a small number of healthy volunteers, typically between 20 and 100 people. The primary purpose is to establish that the vaccine is safe in humans: to identify side effects, characterise the dose range that is both tolerable and produces an immune response, and confirm that no unexpected adverse events occur. Early immunogenicity data showing whether the vaccine triggers antibody production is also collected. Phase 1 trials typically run for six to twelve months.

Phase 2: broadening safety and immunogenicity data

Phase 2 expands to hundreds of participants, often including people from the populations the vaccine is intended to protect, such as older adults for flu vaccines or infants for paediatric vaccines. Safety monitoring continues and more detailed immune response data is collected, including antibody titres, T-cell responses, and durability of response. Dosing schedules are refined. This phase typically runs for one to two years and produces the data needed to design the definitive Phase 3 trial.

Phase 3: the definitive efficacy and safety trial

Phase 3 trials are the largest and most rigorous clinical studies in vaccine development. They typically enrol thousands to tens of thousands of participants in randomised, double-blind, placebo-controlled designs and are powered specifically to demonstrate that the vaccine prevents the target disease. The size of Phase 3 trials also allows detection of adverse events that occur in one in several thousand recipients, providing a much more comprehensive safety picture than the smaller earlier phases. Phase 3 evidence is the primary basis for regulatory approval decisions.

Regulatory review: independent scientific scrutiny

In the UK, the Medicines and Healthcare products Regulatory Agency (MHRA) independently reviews all clinical trial data submitted by the vaccine developer before granting a product licence. The review covers manufacturing quality, consistency between batches, the full safety data from all trial phases, and the efficacy evidence. The MHRA operates separately from manufacturers and does not accept commercial funding from the companies whose products it regulates. It can and regularly does request additional data, impose conditions on approval, or decline to approve.

Post-approval surveillance: monitoring continues indefinitely

Once a vaccine enters routine use, safety monitoring is not finished. The UK Yellow Card scheme allows any healthcare professional or patient to report a suspected adverse vaccine reaction. These reports are continuously analysed by the MHRA. The WHO's VigiBase provides a global picture by aggregating reports from national systems across member countries. Additional active surveillance studies and cohort follow-up programmes provide further data. This ongoing system is sensitive enough to detect adverse events occurring in one in hundreds of thousands of recipients and has led to guidance updates, additional warnings, and product withdrawals when genuine signals have been identified.