As we enter the final few weeks preceding the US election, President Trump is more committed than ever to deliver a vaccine for Covid-19, or at least convince the public that one is very near. It's no secret that the electorate overwhelmingly disapproves his management of the pandemic, so this focus is part of a campaign effort to improve his standing prior to the election.
But how realistic is delivery of an effective vaccine by then? Vaccines normally require about 10 years of testing and more time still to produce at scale. Research on one for Covid-19 began in January of this year. It's only through the coordinated efforts of governments, other funding agencies and the vaccine manufacturers themselves that this record-breaking progress has been possible. As of August 2020, there are 170 vaccine candidates in development. Seven of these are currently in “phase-three” trials. Historically, 85% of vaccine candidates that reach this phase are approved. But it is important to remember that there has never been an approved vaccine for a coronavirus.
Vaccines work by training the body to recognise and respond to the proteins produced by disease-causing organisms, such as a virus or bacteria. They are usually made from small or inactivated doses of the whole disease-casing organism, or the proteins that it produced. These are introduced to the body to provoke the immune system into mounting a response.
Traditional vaccine development goes through six stages. Initially, research is carried out on animals to see if it triggers an immune response. Once this pre-clinical phase is completed, the vaccine is given to a small group of people to establish safety and to determine if any immune response is provoked. This is called “phase-one”. In “phase-two”, expanded safety trials are carried out on hundreds of people to learn more about dosage and safety. Once complete, the vaccine enters “phase-three” – large scale efficacy trials on thousands of individuals. Here side-effects are identified, effectiveness is measured, and its safety is confirmed. The vaccine sponsor then applies to the relevant medical authority for a Biologics Licence Application (BLA), to allow its use in the general population. Once regulation is in place, the vaccine moves on to the production and quality control stages. Other than China’s candidate from CanSino Biologics, which has received limited approval for use within the Chinese Military, and Russia’s potential candidate, there are no candidates that have passed “phase-three” yet.
Vaccines can range in terms of effectiveness. Most routine childhood vaccines are effective to 85%-95% of candidates, but due in part to disease mutations, the seasonal flu vaccine is only around 50% effective. The fact that Covid-19 is a coronavirus has helped speed up vaccine development significantly, as scientists were able to quickly revive vaccine projects from the past as a starting point. The knowledge gained from work carried out on SARS-1 is cited by immunologists and vaccine researchers as a major contributing factor for the speed of the progress made. In addition, Covid-19 is an acute disease, one with severe and sudden conditions derived from an infection that most people can clear on their own. This means that there is a vanquishing immune response that a potential vaccine can aim to induce. More research needs to be carried out to determine whether the virus has mutated. There is a chance that it mutates into a less aggressive strain in order to extend its longevity within a host.
Once a candidate is approved for Covid-19, demand for the vaccine will far outstrip any potential production capacity. The logistics surrounding the synchronised global production and distribution of the eventual vaccine will be enormously complicated. Intellectual property rights between manufacturers and countries will need to be protected. Vaccines also need to be transported globally under very strict conditions to ensure they maintain their potency. New variants of vaccines, such as “mRNA” are significantly easier to manufacture at a large scale. mRNA vaccines trick the body into producing some of the viral proteins itself. mRNAs are the molecules that enact DNA instructions. To produce this kind of vaccine, scientists produce a synthetic version of the mRNA that a virus uses to build its infectious proteins. This is then delivered into the body, which reads it as instructions to build that viral protein, and therefore create some of the virus’ s molecules themselves. The immune system then detects these viral proteins and starts to produce a defensive response. Both Moderna and BioNTech have vaccine candidates that are based on mRNA. Despite the fact that no candidates have been approved yet, millions have already been invested in vaccine manufacturing infrastructure by governments and organisations.
So which candidates are the current front runners? By August, phase three was reached by candidates from Sinovac, Astrazeneca(Oxford University), Moderna/NIAID, Sinoharm, CanSino, BioNTech/Pfizer and Murdoch Children’s Research Facility(University of Melbourne). Taking into account development timeframes, most of these candidates are expected to be available by the end of 2020 or early 2021. But there may still be roadblocks ahead. In September, the AstraZeneca study was paused due to a suspected adverse reaction in a participant. This was described as a routine action to maintain the integrity of the trials by a company spokesperson. Nevertheless, it could impact how quickly efficacy data will be available, integral to any bid to seek emergency use authorisation from regulators.
By November of this year, most of the frontrunner candidates plan to be available for emergency use. We can then expect to hear feedback on effectiveness.
Sources:
Reid.J, Temleman.L, Laboure.M, Deutsche Bank Research, 2 September 2020, Everything We Know about a Covid-19 Vaccine
https://horizon-magazine.eu/article/five-things-you-need-know-about-mrna-vaccines.html
