Our best shot to beat COVID-19 – The science behind the vaccines

Image Credit: Laoise Tarrant

Three COVID-19 vaccines are expected to be administered in Ireland this year, but how exactly does each of them work and how are they different? Aela O’Flynn explains.

The first two weeks of 2021 saw 44% of all cases reported in Ireland since COVID-19 first arrived on our shores. 1 in 67 people on the island tested positive within 14 days. Daily case numbers are at alarming levels, intensive care units are rapidly filling their surge capacity, and healthcare workers who are asymptomatic close contacts are being reintroduced into the workforce.

2021, though not a Happy New Year by any means, does mark the start of the Irish vaccine rollout programme. Paul Reid, CEO of the HSE, calls the vaccine the "key striker" we need to beat the threat of the virus. The three vaccines expected to be distributed in Ireland are produced by Pfizer-BioNTech, Moderna, and Oxford-AstraZeneca. But how exactly does each vaccine work, how effective are they, and how do they differ?

Vaccines generally use a harmless form of a virus or bacteria that teaches the immune system to recognise and respond to features of that bacteria or virus if they appear in the body again. Common vaccine ingredients include preservatives and stabilisers to maintain the safety and effectiveness of the vaccine during transport and storage, tiny traces of agents used to manufacture the vaccine, small amounts of an adjuvant, such as an oil or salt, that strengthens the response of the immune system to the vaccine, and water. 

The first two vaccines to be approved for use in Ireland by the European Medicines Agency (EMA) are Pfizer-BioNTech and Moderna, both of which are mRNA vaccines. Messenger RNA, or mRNA, is part of the genetic code of the virus, and instructs it to make proteins. The vaccines inject mRNA into a patient that then directs the patient's cells to produce “spike” proteins that the virus would normally produce on its outer surface. These spike proteins, called antigens, are harmless to the host, but are used by the immune system to differentiate between cells normally found in the body, and foreign cells. When the immune system recognises these spike proteins as potentially harmful, it prepares a response attack with antibodies and activated T-cells. If this virus later infects the host, the immune system remembers the spike proteins and instructs the body to destroy the viral cells. Clinical trials found that two doses of either vaccine were 95% effective at preventing COVID-19.

mRNA vaccines are an exciting new approach. Despite being studied for decades, this pandemic is the first time that an mRNA vaccine has been approved for use. Traditional vaccines usually use a weak, partial, or inactivated form of a virus, while mRNA vaccines allow us to develop immunity to the virus without ever actually being exposed to it. Although the traditional approach has been successful until now, conventional vaccines have limitations.

mRNA vaccines have three major advantages over traditional vaccines: they are safer, they are often more effective, and they can be more rapidly produced. So why have we not made the switch to mRNA vaccines before now? Until very recently, there were concerns over the efficacy and stability of mRNA vaccines, so pharmaceutical interest was limited. But a recent breakthrough found that if the mRNA is surrounded by a fat coating called a liposome, it is more stable and more useful. Not only that, but when a vaccine needs to be distributed rapidly across continental borders to a significant proportion of the 7 billion people on the planet, the rapid and inexpensive production that mRNA vaccines provide is not only desirable, but indispensable.

These mRNA vaccines do have one major drawback - storage. To maximise shelf-life, both need to be stored in an ultra-cold freezer, the Moderna vaccine between -25 and -15ºC, and the Pfizer-BioNTech vaccine at a heart-stopping -75 to -80ºC. Both can be stored for a limited time between 2 and 8ºC, but the limit is 30 days for Moderna and only five for Pfizer-BioNTech. These rigorous storage protocols are problematic because the allocation of vaccines is currently limited, and we can’t afford to repeat the mistakes of the US with doses expiring in storage before ever being administered.

The Oxford-AstraZeneca vaccine is expected to be approved by the EMA at the end of January. This vaccine also causes host cells to produce viral spike proteins, but using DNA instead of mRNA. The DNA is transported inside a vector called an adenovirus, an altered non-infectious virus which allows the DNA to enter host cells, but cannot itself replicate within them. The DNA travels to the nucleus, the brain of the cell, instructs it to produce mRNA, and produces a mimic of the viral “spike” protein that the cell then displays on its surface.

The Oxford-AstraZeneca vaccine has an advantage due to its relative ease of storage. It can be stored in a normal fridge, which allows the possibility for this vaccine to be distributed in general practice and pharmacies. It is also cheaper to produce, at an expected cost of $3 per dose. Clinical trials found that the two-dose regimen of the Oxford-AstraZeneca vaccine was 70.4% effective on average between two possible dosages, but the combination of an initial half dose followed by a full second dose may be up to 90% effective.

Despite promising clinical trial data of the efficacy and safety of these three vaccines, a number of questions remain. As these vaccines have been developed so rapidly, we do not yet know how long their protection persists. Will there be a need for further booster doses? We are also awaiting conclusive data over whether the vaccine prevents transmission of the virus, meaning we are still unsure whether you can be an asymptomatic carrier of COVID-19 after vaccination. The vaccine most likely does significantly lower the risk of transmission, but conclusive evidence has not yet been accumulated.

The promise of vaccination is cause for great optimism. These vaccines were developed at a remarkable speed as a result of outstanding cross-border collaboration that builds upon decades of research in vaccinology, and they have undergone the same rigorous safety testing that any other vaccine would. While some answers remain elusive, we do know that these three vaccines bring us closer than we have ever been to a world free from the threat of COVID-19.