In the last 48 hours we have heard news of the emergence of the B.1.1.529 variant of Sars-Cov-2 in South Africa, while at home the National Immunisation Advisory Committee (Niac) has recommended Covid-19 vaccine “boosters” for everyone 16 years and older. The scientific evidence in favour of booster vaccines is very strong and is now more important than ever with the emergence of this worrying new variant.
Covid-19 is once again out of control in many countries in Europe. Ireland is near the top of the list in terms of number of cases per 100,000 people. This has been fuelled by the easing of restrictions, with a return to larger gatherings in indoor venues. It is also a reflection of breakthrough infections in fully vaccinated individuals as result of waning immunity post-vaccination. However, a disproportionately high number of intensive care admissions and deaths from Covid-19 in Ireland are in the small minority of people who are not fully vaccinated.
Countries with the highest vaccine coverage, and Ireland is near the top of this list, have the lowest death rate from Covid-19. So, with such a high vaccine uptake, why are there so many cases of Covid-19 in Ireland and why are our hospitals once again under pressure and facing another crisis as we head into winter?
The current Covid-19 vaccines were designed to protect against the Wuhan strain of Sars-Cov-2 and their efficacy was tested in phase-three clinical trials against symptomatic Covid-19 disease, but not against Sars-Cov-2 infection, using a two-dose schedule, or one dose in the case of the Johnson & Johnson (J&J) vaccine.
The vaccine manufactures did not have huge insight into how many vaccine doses would be optimum for protection across all human age groups and did not have time to do the long-term studies to see if the immune responses persisted for months or years after vaccination. Furthermore, they did not predict that the virus would mutate so readily and escape much of the protective effects of the vaccine-induced immune response.
The key positive factor is that several manufactures developed, in less than a year, highly effective vaccines that have had a huge impact on Sars-Cov-2 infection outcomes and deaths from Covid-19. It is estimated that Covid-19 vaccines have averted more than 250,000 deaths in the US and more than 4,000 deaths in Israel. With a higher vaccine uptake in Ireland, Covid-19 vaccines have probably saved a proportionally higher number of lives in this country.
What we know now from real-world data – and did not know when the vaccines were first introduced – is that the effectiveness of AstraZeneca, J&J, Pfizer and Moderna Covid-19 vaccines decline three-six months after immunisation, even with two doses. This reflects a relatively rapid decline in virus-neutralising antibodies in the circulation after vaccination. However, there is convincing scientific evidence that antibody responses are significantly enhanced after booster doses with Covid-19 vaccines.
Although vaccine effectiveness declines relatively rapidly after immunisation in all adult age groups, protection can be dramatically restored and enhanced by booster vaccination. A recent study from Public Health England found that vaccine effectiveness against symptomatic Covid-19 dropped to 40 per cent five months after two doses of the AstraZeneca vaccine and to 60 per cent for the Pfizer vaccine. However, vaccine effectiveness against symptomatic Covid-19 was elevated to 93-94 per cent in both cohorts after a single booster dose with the Pfizer vaccine and similar results for the Pfizer vaccine were reported from Israel.
The scientific evidence for booster vaccination is very strong
Israel introduced the booster programme for everyone over 12 at the end of August and the seven-day average number of Covid-19 cases dramatically declined from a peak of more than 11,000 in mid-September to about 400 this week.
Although we do not know yet whether, or how soon, immunity will wane after boosting, the substantial elevation of the neutralising antibody responses reported after the third dose suggests that vaccine effectiveness will persist significantly longer than it did after two doses.
New variants
The biggest variable that will affect future effectiveness of Covid-19 vaccines is the emergence of new variants that completely escape immunity induced with the current vaccines. The B.1.1.529 variant identified in South Africa, Botswana and Hong Kong has more than 30 mutations in the spike protein (the target for the protective antibodies), many more than in any previous variant. While it is too early to predict, it is possible that the B.1.1.529 variant will evade at least some of the protective effects of vaccine-induced antibodies and may also be as transmissible as the Delta variant.
Booster doses with Covid-19 mRNA vaccines have been reported to significantly enhance protective antibody responses to Alpha, Beta and Delta variants and may also enhance antibodies against the B.1.1.529 variant. This emphasises the urgency of implementing and completing the booster programme for all adults in the country.
The vaccine manufactures have developed and are testing new Covid-19 vaccines specifically designed to protect against the Delta and Beta variant, but attention will now have to turn to the B.1.1.529 variant. Once approved by regulatory agencies, these updated vaccines will likely replace the existing vaccines. We may need yearly Covid-19 vaccines to counter the emergence of all variants of concern, analogous to the seasonal influenza vaccine.
The scientific evidence for booster vaccination is very strong and while Covid-19 vaccines, like all others, are not devoid of side effects, a risk-benefit analysis must favour vaccination above a potentially life-threatening infectious disease.
Right now, the number of cases of Covid-19 per 100,000 in Ireland is highest in primary school children, who are unvaccinated, followed by the 19-24, 25-34 and 35-44 age groups. Plans to boost every adult in the country should be implemented as soon as possible to avert further escalation in cases and hospitalisation from Covid-19. Following approval by the European Medicines Agency this week, the Pfizer paediatric Covid-19 vaccine will probably be recommended by Niac for five- to 11-year-olds.
Although longer intervals between vaccine doses can broaden the antibody response, the risk-benefit analysis may favour boosting adults at four, rather than five-six, months after the two-dose vaccines. Reducing the interval to four months would allow all recipients of the AstraZeneca vaccine to be boosted and immune before the inevitable surge in cases after Christmas.
Averting another lockdown will require: 1) the HSE to expedite and streamline administration of booster vaccines; 2) the Government to rapidly put in place appropriate measures to prevent importation of the B.1.1.529 variant; 3) the National Public Health Emergency team to overcome their reluctance to fully embrace antigen testing; 4) unvaccinated adults to recognise the risks to themselves and to others of not being vaccinated; and 5) the public to embrace the booster programme, reduce social interactions in the lead-up to Christmas and adhere to public health advice. Without this combination of mitigation approaches, we must expect a return to the situation we experienced last January, and nobody wants that.
Kingston Mills is Professor of Experimental Immunology and Academic Director Trinity Biomedical Sciences Institute at Trinity College Dublin