Seán Dunphy discusses recent developments in COVID-19 vaccines.
Vaccine development is complex and often takes 10 to 15 years of research. With this in mind the scientific response to the Covid-19 pandemic is remarkable. In a single year, 54 Covid-19 vaccines have been brought to human trials, and 13 of these are in the final phase of trials before seeking government approval. An innovation in vaccine technology has helped this rapid response: the advent of messenger RNA (mRNA) vaccines.
Two vaccine candidates in particular, both mRNA vaccines, have gained significant media attention following the release of encouraging preliminary phase III results. On November 9th, pharmaceutical giant Pfizer in collaboration with BioNtech announced over 90 percent efficacy of their vaccine, which was quickly followed by a similar press release from biotech company Moderna on November 16th celebrating the 94.5 percent efficacy of their candidate.
Both vaccines are based on mRNA templates for the SARS-CoV-2 spike protein and both vaccines have estimated efficacies of 94 percent following phase III trials of more than 30,000 volunteers. Neither trial revealed any safety concerns or side effects beyond temporary fatigue and muscle aches, which are often associated with mounting an immune reaction in response to a vaccine. Since flu vaccines are generally between 40 and 60 percent effective, 94 percent efficacy is remarkable, and its consistency across two differing mRNA vaccines represents great potential for mRNA vaccines going forward. However, as promising as these results are, mRNA vaccines have their own challenges.
All vaccines function in a similar manner, by mimicking an infection to train a specific immune response. This dramatically reduces the time taken for the body to react to and fight off a real infection should one occur. In the past, vaccines against viral infections have often followed one of two moulds – attenuated vaccines or inactivated vaccines – both consisting of viral material grown in mammalian cells. mRNA vaccines differ in their lack of any viral material. Instead, mRNA acts as a temporary template for our cells to generate their own copies of SARS-CoV-2 proteins which in turn stimulates our immune response against the virus.
Since flu vaccines are generally between 40 and 60 percent effective, 94 percent efficacy is remarkable.
One of the major advantages of mRNA is that it can be made synthetically, removing safety concerns around using mammalian cells to grow viruses for vaccines in the lab. In addition, mRNA synthesis is much quicker than growing actual viruses, as is reflected in Pfizer and Moderna beating their competitors to releasing efficacy measures. The ease of this synthetic approach will allow for a quicker scaling up of production.
The major challenge associated with mRNA is its fragility – it requires storage at very low temperatures. The excitement following Pfizer’s announcement of its preliminary results was quickly quenched by the challenges faced in maintaining and transporting the vaccine in ultra-cold storage (-60C—80C). Moderna’s vaccine in contrast is stable at -20C for up to 6 months, and can even be kept at normal refrigeration temperatures for 30 days. This is likely due to differences in the nanoparticles coating the mRNA in the vaccines. These nanoparticles, often lipids, are used to stabilize the fragile RNA, raising the temperatures that they can be stored at.
mRNA acts as a temporary template for our cells to generate their own copies of SARS-CoV-2 proteins which in turn stimulates our immune response against the virus.
However, even transport at -20C is a costly logistical challenge, and one that is not shared with the AstraZeneca-Oxford University attenuated vaccine. Unlike Pfizer’s and Moderna’s mRNA vaccines, this AstraZeneca vaccine is stable at normal refrigeration temperatures for more than 6 months.
The AstraZeneca vaccine is based on a relatively harmless adenovirus that causes colds in chimpanzees, which has been altered to feature the SARS-CoV-2 spike protein on its surface. It has the added advantage of its low cost. A full course of this vaccine is expected to cost just £6, one fifth of the cost of either mRNA vaccine.
In a similar suit to Moderna and Pfizer before them, AstraZeneca and Oxford announced the preliminary measure of efficacy for their vaccine candidate this week, with estimated efficacies between 62 percent and 90 per cent depending on the vaccination schedule. The low cost and ease of storage of the AstraZeneca vaccine may prove vital to low and middle income countries in particular, but there is still a lot left unknown. AstraZeneca’s press release was not accompanied by evidence of the data, leaving doubts around the number of COVID-19 cases contributing to the measure of efficacy. Questions arise particularly for the 90 per cent efficacy measure, given that it is based on a smaller number of participants that were mistakenly given a half dose initially due to a calculation error. AstraZeneca have since stated that they will likely conduct another trial to follow up on this more effective, albeit accidental, dosage. The press release similarly reported no safety data beyond stating that they had not experienced any serious safety events.
Pfizer on the other hand have already presented a first set of complete results of a Phase 3 trial of 44,000 participants across a wide demographic. These results included a 94 percent efficacy in those older than 65, a crucial outcome given they are the most at risk group. These results were accompanied by an announcement that they were ready to submit safety data to the FDA. There’s no doubt that mRNA vaccines are a valuable innovation, and may be invaluable for treating high risk demographic groups or those who are unable to receive attenuated vaccines like the clinically immunosuppressed. However, the low cost and relative ease of distribution of more traditional vaccines demonstrates a role for a variety of effective vaccines when tackling the CoVID-19 pandemic. In practice, effective distribution and administration of vaccines will likely involve taking advantage of the strengths of many vaccines. This could include administering mRNA vaccines, like Pfizer’s, to those who are more centralized and at greater risk such as over 65’s and healthcare workers, and administering attenuated vaccines like AstraZeneca’s to those who are not as vulnerable. As well as balancing the relative cost of the vaccines with the differing needs of each demographic group, this distribution of manufacturing across multiple companies should allow quicker scaling of production to more quickly meet the populations vaccination needs.
Written by Seán Dunphy and edited by Ailie McWhinnie.