Dr Kevin McCarroll
Medical Matters
The Covid-19 pandemic has now infected more than 15 million people globally and claimed the lives of more than 600,000. While the incidence in Ireland remains low, significant spikes in the number of cases in parts of the US, UK and Australia are a reminder of the need for ongoing vigilance and restrictions.
Indeed, unfortunately, without a vaccine the limitations on some of the liberties we take for granted will likely remain in place.
Currently, there are more than 137 candidates for vaccines in laboratory development with a further 23 in clinical studies. Promisingly, three studies where vaccines were administered to healthy people have recently shown very positive results.
Just last week, the Oxford group in conjunction with the pharmaceutical AstraZeneca published the results of their latest trial in The Lancet. Their vaccine contains the spike protein of the SARS-CoV-2 virus packaged into a weakened cold virus. When administered to 543 healthy adults they found that it triggered two immune responses with peak antibodies detected at 28 days as well as an earlier rise in a specific type of immune cell (T cells).
Replication
Antibodies binding to the virus can prevent it from latching onto and invading cells. However, T cells are also very important as they specifically recognise virus infected cells and kill them preventing further replication of the virus.
Some participants in the trial received a booster dose of vaccine which led to them developing neutralising antibodies. Importantly, side effects were not serious though included local pain at the injection site, headaches and fever which resolved quickly and were relieved with paracetamol.
The vaccine is now entering a phase 3 clinical trial in which about 4,000 participants enrolled in the UK and is also being extended to South Africa and Brazil.
Vaccine researchers have cited an 80% chance of a successful result and the UK government has also secured a deal for supply of about 90 million doses should the vaccine be approved.
The vaccine trials to date have also not included older adults or those who are immunocompromised”
The results of another promising vaccine trial in Wuhan, China were also published last week. They used a genetic fragment of the coronavirus which they packaged into a non-replicating adenovirus. When administered to 382 adults, there was a significant neutralising antibody response after 27 days.
Finally, promising news also came last week from the US based company (Moderna) which published its early stage clinical trial in The New England Journal of Medicine. Their vaccine contains a fragment of genetic material that encodes the SARS-CoV-2 spike protein which allows it to attach to cells. Their study found that in 45 healthy adults who were administered the vaccine 28 days apart, there was a significant neutralising antibody response.
While results so far are encouraging, the real test will be whether or not the immune responses elicited are sufficient to prevent Covid-19 or significantly reduce its severity.
It also remains unclear how long any immunity might last. For example, in a recent study of patients affected with SARS- CoV-2 there was a significant drop in antibody levels at three months. However, vaccine responses may be greater and the immune system has a memory, (particularly with T cells) that can lead to a quicker reactivation of antibody production after virus exposure.
The vaccine trials to date have also not included older adults or those who are immunocompromised, groups that are less likely to elicit the same immune response.
It has been proposed that to speed up vaccine development ‘challenger’ trials could be done. This would involve deliberately exposing people to the coronavirus after vaccination to gauge how effective it is. Clearly, this would pose the risk of serious infection for some and there would be logistical problems as to where people would be inoculated and what strain of virus to use.
Nonetheless, it’s very likely that before the end of the year, there will be conclusive results on some phase 3 clinical trials. However, even if successful, they will need to go through fast track approval by the regulatory authorities. Manufacture, distribution and also vaccine administration poses a major logistical challenge given the sheer numbers involved. However, all going well, the prospect of vaccination for most people could begin in early to mid-2021.
There is always the potential for serious but less frequent side effects to emerge with vaccination at large”
For a vaccination program to be successful at reducing spread, immunity will need to be conferred on about 60-70% of the population, so it’s crucial too that vaccine uptake is high.
Finally, while clinical trials can involve up to several thousand people, there is always the potential for serious but less frequent side effects to emerge with vaccination at large. However, with several candidate vaccines in trials, we may well have several options available to us.
Dr Kevin McCarroll is a Consultant Physician in Geriatric Medicine, St James’s Hospital, Dublin.