Thanks to vaccines it looks like we will win the war against Covid-19, but the rules of engagement have changed as a result of the emergence of variants, and it could be a long and rocky road before we are out of the woods and back to “normality”.
Many viruses are susceptible to mutation as they rapidly multiply inside human cells, allowing new variants to emerge. This has facilitated more transmissible virus variants, notably in the UK, South Africa and Brazil, to become dominant.
The UK B117 variant of SARS-CoV2 – the virus that causes Covid-19 disease – is already the dominant strain in Ireland and the UK, where there are also sporadic cases of the B1351 variant from South Africa and a new variant recently found in Bristol.
There is another insidious consequence of these mutations. Antibodies that neutralise the virus do so by interfering with the binding of the virus to receptors on human cells. The part of the virus that does this – the spike protein – is what changes in the variants. This means that antibodies generated against the original virus, through previous infection or vaccination may not have the ability to neutralise the new variant.
This is a major issue with influenza vaccines, which need to be changed every year to accommodate the evolution of the influenza virus. It is set to become an issue for the Covid-19 vaccines, though perhaps not to the same extent.
Good news has emerged from Israel, which has the highest vaccine coverage in the world. Two doses of the Pfizer-BioNTech vaccine significantly reduced the number of people getting Covid-19; the effectiveness in the whole adult population was estimated to be 90-95 per cent. People who became infected after a single vaccine dose had around a four-fold lower viral load – the amount of virus in their upper respiratory tract* – than unvaccinated individuals. This suggests that vaccination may reduce virus transmission to others. This may be even more dramatic after two doses.
Ireland should have enough doses of high efficacy Covid-19 vaccines to immunise the whole adult population this year. Once the over- 65s are vaccinated the number of deaths from Covid-19 should decrease significantly.
Travel restrictions
The next challenge is to ensure that we do not re-import the virus from countries where Covid-19 is not controlled because of vaccine availability or logistic issues. We need properly-enforced travel restrictions, especially to deal with more transmissible virus variants.
The Pfizer-BioNTech, Moderna and Novavax vaccines each have around 95 per cent efficacy against the original virus, but data from the Novavax phase-three trial showed that this dropped to 85 per cent against the UK B117 variant and 60 per cent for the South African variant.
The efficacy of the soon-to-be-approved Johnson&Johnson vaccine was 72 per cent after a single dose in the US, where the original virus strain is prevalent, but only 57 per cent in South Africa where the South African variant is dominant.
The reported efficacy of two full doses of Oxford-AstraZeneca vaccine is 62 per cent against Covid-19 disease (later studies showed that one dose reduced the number of infections by 67 per cent), but, worryingly, this vaccine did not prevent mild or moderate Covid-19 disease caused by the South African variant. South Africa has paused the rollout of this vaccine.
Recent data on a new variant found in Bristol, which is like the original UK B117 variant but with the key E484k mutation common to the South African and Brazilian variants, suggests that it may impact on vaccine efficacy.
Previous infection or vaccination can confer protective immunity, but this can be evaded by mutated viruses, such as the South African, Brazilian or Bristol variants.
Studies in the city of Manaus in Brazil revealed a sharp decline in infection rates once 70 per cent of the population had been infected. However, there was a resurgence of infections after the emergence of the Brazilian variant.
Modern technologies
Luckily the modern technologies for vaccine production, especially for mRNA vaccines, will facilitate rapid development and manufacture of second generation Covid-19 vaccines against new variants or mixtures of variants. This is already under way, with new vaccines expected to be manufactured and tested within a few months.
While the new vaccines will not require large scale efficacy testing they will require safety testing and careful logistic planning by health authorities and flexibility in vaccine administration schedules. These are not insurmountable issues.
Vaccine-manufacturing companies have developed a range of highly successful Covid-19 vaccines in less than a year. This would not have been possible without the decades of basic scientific research in immunology, virology and vaccinology.
This research has helped to predict that neutralising antibodies along with T cells were key components of immune response that the vaccine needed to generate to confer protection. It also predicted that the SARS-CoV-2 spike protein was the target for the protective immune responses. Research also helped develop effective vaccine approaches for inducing protective antibodies and T cells.
The next steps will be to develop new vaccines that prevent infection with emerging virus variants, as well as prevent infection and transmission of the existing virus strains.
Vaccines will also need to confer long-term protection (against all variants) through potent immunological memory. The latter requires more research, but the vaccine companies and their academic partners are already tackling the variants.
The major question that everyone wants answered is when will we get back to normality? When can we go to a football or rugby match, or for a holiday in the sun?
There is too much uncertainty at present to make predictions. The original announcement that all over 70-year-olds in Ireland will be vaccinated by the end of March cannot now be achieved. This prediction seems to have been based on initial over-optimism around vaccine efficacy, approval or supply.
The National Immunisation Advisory Committee subsequently making the correct decision to recommend the most effective vaccines for the most vulnerable also had an impact.
Predictions
We also need to be realistic about predictions of reaching herd immunity in Ireland this year.
Herd immunity would require induction of immune responses against all circulating Covid-19 virus variants in 70 per cent of the population, including children.
While clinical trials are ongoing, no Covid-19 vaccine has yet been licensed for use in children, and 24 per cent of the Irish population is under 18. Although the current evidence shows that children are not a major source of virus transmission, this may not be the case for more transmissible variants.
Finally, to reach effective herd immunity the vaccines need to prevent infection as well as Covid-19 disease, and while the signs are encouraging we await further data.
The key take-home message is this: effective vaccines, which have been facilitated by scientific breakthroughs, are coming to the rescue. Yet a lot more work must be done by scientists, governments and the public.
Kingston Mills is professor of experimental immunology and academic director at Trinity Biomedical Sciences Institute, Trinity College Dublin
*This article was ammended on 13th February 2021
