Warp speed to a COVID-19 vaccine? The race is on!
In the fight against coronavirus, an effective vaccination could be the game-changer that the world is waiting for. It typically takes several years to develop a new vaccine, so how close are we to finding a real vaccination for coronavirus, and how might this work to protect us?
During these unprecedented times, the prospect of an effective vaccine against COVID-19 is rarely out of the news, with trials underway on a global scale. There are currently estimated to be over 180 coronavirus vaccines in various stages of development, including several now in the latter stages of clinical trials.
How do viruses work?
Viruses, like SARS-CoV2 which causes COVID-19, are dependent on host cells within our bodies to reproduce and spread.
Viruses have special ‘spike’ proteins on their surfaces that act as ‘molecular keys’, enabling the virus to enter specific cells of the body and establish infection. Once inside, this intruder takes over, hi-jacking the cellular resources ordinarily used for cell growth and repair to make copies of itself. These new viral copies go on to infect neighbouring cells until our immune systems step in.
A brief introduction to immunity
The first time we are infected by a disease-causing agent or ‘pathogen’ such as a virus, our immune system has no way of recognising it. Within days we begin to experience disease symptoms and, depending on the infection, we may even become seriously ill.
During this time, the immune system starts to fight back, generating a specific response targeted against pathogen-specific ‘markers’ known as ‘antigens’. Specialised white blood cells called B cells begin to make large amounts of antibodies, and another type of ‘killer T cells’ recognise and kill infected cells. These serve to limit the spread of and resolve the infection, so that a full recovery can be made as quickly as possible.
After this initial response, so-called “memory cells” usually persist, in case you become infected by the same agent again.
Know your enemy: educating the immune system
Vaccines work by tricking the immune system into mounting a response to a pathogen in the absence of infection.
Vaccines have moved on considerably since the first ‘vaccine’ against smallpox, based on the work of Edward Jenner during the eighteenth century. Dr Jenner observed that milkmaids who developed cowpox (caused by a similar but weaker virus to smallpox) never contracted smallpox. These observations led him to experiment in vaccinating patients including an eight-year-old boy with cowpox virus obtained from pus-filled blisters on a young milkmaid’s hand, before later challenging them with smallpox virus.
How are vaccines developed?
Vaccine science or ‘vaccinology’ has moved on since these early days. Candidate vaccines undergo extensive pre-clinical testing in human laboratory-grown cells and laboratory animals before clinical studies involving human volunteers begin.
Clinical testing is usually split into three highly-regulated phases. Severe reactions during any phase are highlighted and investigated by a national regulatory agency, such as The Medicines and Healthcare Products Regulatory Authority (MHRA).
Phase One tests a small group (usually up to 100) of healthy volunteers to identify any safety concerns and establish an effective dosage.
Phase Two tests up to several hundred volunteers, looking for side effects and the ability of the vaccine to trigger an immune response.
Phase Three tests thousands of volunteers, aiming to prove that the vaccine triggers an immune response needed to prevent disease, uncover rarer side effects and provide evidence that the vaccine could reduce the number of disease cases.
Clinical evidence is reviewed by experts before a licence is granted for the vaccine’s widespread use. In the interest of accelerating the development of a vaccine for COVID-19, many national healthcare regulators have allowed Phase Two and Three studies to be combined.
The COVID-19 vaccine - meet the contenders
There are currently a handful of vaccines in Phase Three clinical trials. There are many ways in which vaccines can be made and with serious contenders in all categories, the following is a non-exhaustive list:
‘Inactivated’ vaccines use a heat or chemically-treated version of the virus, and this method has been used to produce certain Polio and flu vaccines. It requires the right amount of heat or chemical to destroy infectivity, as too much could change the virus proteins, rendering the vaccine ineffective. There are Chinese inactivated vaccine candidates under development, including the State-owned SINOPHARM’s ‘Vero-Cell’, in Phase Three trials and expected to complete in summer 2021.
‘Attenuated’ vaccines are more similar to the strategy pioneered by Jenner, using versions of the virus that are weakened until they lose their ability to establish disease. The chicken pox vaccine and some flu vaccines use this method. Whilst there are currently no true COVID-19 vaccines being developed in this way, in Australia and the Netherlands two Phase Three studies are looking at whether the BCG vaccine, an attenuated vaccine for tuberculosis, could provide some protection against COVID-19.
‘Subunit’ vaccines involve using pieces of the virus. This fragment could be a bacterial toxin or even a laboratory-made part of a pathogen. They are sometimes given in combination with an immune-boosting agent called an ‘adjuvant’ to trigger a stronger immune response. These include the hepatitis B vaccine along with the Human Papilloma Virus vaccine, that is now being offered to adolescent girls to prevent cervical cancer. American developer Novavax has a COVID-19 candidate in Phases One-Two of clinical trials.
More sophisticated approaches are described below:
Viral vector vaccines involve removing a ‘gene’ or instruction for a viral spike protein from one virus and gluing it into another, harmless virus. When delivered to the recipient, this will trigger a protective response. This method has been used to deliver an Ebola vaccine.
The AstraZeneca vaccine (or Oxford vaccine, as it is sometimes known), is made in this way, using a modified chimpanzee cold virus to deliver the SARS-Cov2 spike protein into the body. This vaccine is currently in Phase Three trials at various sites around the world. Initial data is encouraging, and it is currently considered to be one of the front-runners in the vaccine race, but it might not be the ‘winner’. Trials have now been paused twice to investigate possible rare reactions.
Another example is Sputnik V from Russia’s Gamleya Institute, which uses a human cold virus engineered to contain a SARS-Cov2 spike protein. This has been approved for distribution in Russia despite only having been tested in a small number of people in early stage trials lasting just two months!
mRNA and DNA vaccines mimic infection by delivering instructions to build viral proteins to recipients’ cells. There currently are no vaccines in either of these categories that have been approved for use in humans. This has not deterred ModernaTx, a US-based company that is working in collaboration with the US National Institute of Allergy and Infectious Disease to develop a mRNA vaccine to prevent the entry of the COVID-19 virus into human cells. This vaccine has bypassed all studies in animals, instead jumping directly into a Phase One trial of 45 participants. A Phase Three study of 30,000 participants in the US is now in progress.
What should success look like?
In addition to providing protection through neutralising antibodies and T cells, an effective vaccine should also induce ‘memory,’ to prevent a person from being re-infected many years later.
For some vaccines one shot is all it takes, but others require boosters. In children, where there are national childhood immunisation programmes this could be achievable, however for adults with no such initiatives in place it would require concerted effort.
Vaccine development is a long and often winding road that can be filled with obstacles. Usually it takes more than 10 years to develop a vaccine, but the Mumps and Ebola vaccines that developed in four and five years respectively are the current record breakers. Let us hope that the COVID-19 vaccine will be next.
Keeping well in the fight against coronavirus
In the meantime, keeping as well as possible is now more important than ever. The onset of winter will bring with it all the usual winter illnesses despite this pandemic; meaning that the risk of complications from seasonal flu has by no means gone away. If you have a long-term condition such as scleroderma you are likely to be offered a free flu jab, which still offers the best protection against the flu viruses in circulation. Although the vaccine is generally recommended there is actually no obligation, and there will be a small number of people for whom this is not suitable for various reasons. Please click here to find out everything you need to know about the flu jab. If you have any comments or queries, please contact us.