What are vaccines, and how do we know that they are safe?

Vaccination is seen as the ‘gold standard’ in the fight against viruses, and there are hundreds of clinical development programmes globally looking to develop safe and effective vaccines. This has caused unprecedented levels of collaboration within the industry — and with regulators — to ensure viable candidates are accelerated through the development gateways.

The UK life sciences sector and the government have been particularly active in this area, with at least one of the lead vaccine candidates being developed in the UK and likely to be approved by the end of 2020 by the MHRA. The types of vaccines in development may be grouped and summarised as below:

  • Whole virus vaccines — typically referred to as ‘first generation’ that are partially inactivated viruses whose virulence and infectivity has been diminished to make them safe, but sufficiently intact to remain efficacious and allow the body to produce antibodies.
  • Protein-based vaccines — isolating and producing large quantities of the virus surface proteins to train the immune system to respond and produce antibodies following injection.
  • Virus-vector vaccines — isolating the virus genetic code (RNA) and delivering it into cells so that the host can produce non-virulent particles that the body’s immune system raises antibodies against.
  • Genetic vaccines — isolating the virus’ genetic sequence to produce viral proteins against which the body produces antibodies.
  • Existing repurposed vaccines — relying on the genetic similarities within human infective viruses to illicit a favourable immune response.

Regardless of the type or mode of action, all pharmaceutical products must pass through a series of rigorous safety and quality assessments known as clinical trials — taking place in three stages. The purpose of clinical trials is to undertake controlled assessments and provide statistically significant assurance that the vaccine:

  • Results in the production of antibodies in a target population, noting that there will always be some non-responders that must be quantified.
  • Is safe and does not result in adverse immunity following a period of monitoring. Known side effects and their frequency must be statistically evaluated and documented.
  • Continues to provide immunity and evidence safety over a defined period.

Such clinical trials are highly controlled and can normally take up to ten years to complete —after which a vaccine may be manufactured.

Whilst such lengthy study and assessment periods are necessary to monitor long term safety — as well as any potential drug-drug interactions — it’s important to note that most adverse events are observed within a 10-12-week period after adminstration.

As vaccines are intended to be given to people who are fit and well — rather than those already infected — the majority of such adverse events are mild fever, headache and soreness at the injection site, and must be monitored in a target population of varying demographics.

The clinical studies are therefore designed to ensure vaccine safety and efficacy is to the highest standards. The burden of proof is always on the vaccine developer and regulators to ensure checks and controls are in place, assuring data integrity.

Along with the government’s underwriting of the financial risks, innovators and vaccine developers have had access to uncapped resources, and as such have been able to expedite the development of candidate vaccines by more than ten-fold — something that would have been considered entirely impossible just one year ago.

Leading clinical trials have already been unblinded, and with the likelihood of at least two candidates being approved by the MHRA by the end of December 2020 — with millions of doses already having been manufactured at risk throughout the year — it’s clear that this is the beginning of the end of the coronavirus pandemic.