The Covid-19 vaccines are working. While clinical trials showed that the vaccines confer protection against Covid-19 disease, real-world data from Israel, the UK and the US suggests that certain vaccines can also prevent infection with Sars-CoV-2 and may therefore stop transmission of the virus.
A recent report from the US Centre for Disease Control estimated that two doses of the Pfizer or Moderna vaccine were 90 per cent effective at preventing Sars-CoV-2 infection in healthcare and other frontline workers, while vaccine effectiveness for a single dose was 80 per cent. Data in Ireland has indicated that the vaccines have substantially reduced the numbers of cases of Covid-19 among healthcare workers and nursing home residents, two cohorts with hitherto high incidence of Covid-19.
While the emerging data on real-world use of the vaccines is extremely encouraging, we are not out of the woods just yet. Like most other EU countries, the rate of vaccine administration in Ireland has been constrained by vaccine supply and has recently been exacerbated by modification to plans resulting from rare blood clotting events linked with the Oxford-AstraZeneca and Johnson & Johnson (J&J) vaccines. The number of cases is relatively small, about 1/1,000,0000 for the J&J vaccine and about 1/100,000 for the AstraZeneca vaccine.
There are plausible scientific explanations for the development of vaccine-associated thrombosis and thrombocytopenia, including the development of antibodies against platelet factor-4. However, there is rather limited scientific evidence to support the use of the AstraZeneca vaccine in 60-69 year olds and not in other age groups. The clotting events are dominant in those under 50 but have been reported across all age groups, including the over-60s.
While the benefits of the vaccines still outweigh the risks, the reported adverse events and their handling by our authorities may have a negative impact on confidence and therefore uptake of Covid-19 vaccines in Ireland.
Public confidence
Initially, the National Immunisation Advisory Committee (Niac) recommended that people over 70 should not be given the AstraZeneca vaccine, citing lack of data in older age groups, but also influenced by the higher efficacy of the mRNA vaccines from Pfizer and Moderna. When the blood clot events resulted in suspension, and subsequent resumption of the AstraZeneca vaccine, Niac recommended not giving this vaccine to those under 60. Consequently, the 60-69 age group are shoehorned into taking the AstraZeneca vaccine.
The comments from senior politicians that 60-69 year olds who do not register for the AstraZeneca vaccine would be consigned to the end of the queue smack of coercion, and do not instil public confidence in this vaccination strategy.
While totally endorsing the huge benefits of the vaccines over the risks of side effects, some risks are real, albeit very rare, and not every vaccine confers protection in every recipient, with some vaccines working better than others. The Medical Council guidelines make it clear that recipients of medicines (including vaccines) have a right to make an informed choice and should be provided with all the information necessary for decision-making, including details on possible adverse reactions, efficacy and alternatives. The appropriate information should be clearly communicated to every individual prior to vaccination and the current plans for vaccinating the 60-69 age cohort deserves wider debate.
Older people have a relatively high risk of developing Covid-19 disease that may lead to hospitalisation (and there have been 255 deaths in Ireland from Covid-19 in people aged 55-64 and 740 deaths in 65-74 year olds), yet Niac and the Health Service Executive have decreed that 60-69 year olds should receive a vaccine with lower efficacy than the mRNA vaccines, especially against variants of concern.
The AstraZeneca vaccine is clearly working in the UK, where there is good evidence that it can prevent Covid-19 disease, including that caused by the UK B.117 variant. However, a small clinical trial carried out in South Africa showed that the AstraZeneca vaccine had only 10 per cent efficacy against mild or moderate disease caused by the South African B.1.351 variant. The authors of this report published their findings in the New England Journal of Medicine on March 19th, stating that “Deliberations on the utility of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine also need to be made in the context of ongoing global spread and community transmission of the B.1.351 variant.” As a consequence, South Africa stopped using this vaccine. The US has never licensed it and Denmark has suspended its use after the clotting issues, perhaps because it astutely acquired extra doses of the Pfizer vaccine.
Virus variants
Clinical trials or real-word data have indicated that the Pfizer, J&J and Novavax vaccines can confer protection, albeit reduced, against Covid-19 caused by the South African B.1.351 variant. The Novavax vaccine, based on more traditional protein subunit technology, had 95 per cent efficacy against the original Sars-CoV2 in phase-3 clinical trials. Another vaccine from CureVac, based on the same mRNA technology as the Pfizer and Moderna vaccines, is also expected to be highly effective. The Novavax and CureVac vaccines are undergoing rolling reviews by the European Medicines Agency, and both can be stored at fridge temperature. Together with the vaccines from Pfizer, Moderna and J&J, if licensed by the EMA, they should provide more than enough doses to cover our entire Irish population.
Virus variants can emerge though selective pressure from the immune responses generated by infection or vaccination. Viruses with mutations in the regions of the virus targeted by neutralising antibodies have a selective advantage because they can escape the neutralising effect of the antibody. This is a particular problem in immune-suppressed individuals or following immunisation with a vaccine that does not completely prevent infection. This provides a convincing argument why high-efficacy vaccines should be used where possible to prevent infection as well as disease, especially in vulnerable populations.
France and Germany have already recommended that individuals under 55 or 60 respectively who received a first dose of the AstraZeneca vaccine should get a second dose of an mRNA vaccine. It would be reassuring if the Irish authorities took their lead from this and prioritised individuals in the 60-69 age group for booster doses of the highly effective mRNA vaccines, including new versions of the vaccines, under development and testing, for protection against virus variants of concern. This would ensure that one age group is not locked into a vaccine that is beset by repeated failure to deliver promised supplies, is associated with rare clotting events, and has limited efficacy against variants of concern that are gaining a foothold in many European countries, including Ireland.
Kingston Mills is professor of experimental immunology and academic director at Trinity Biomedical Sciences Institute, Trinity College Dublin