We watched with horror as the death toll from the Pandemic unfolded. Most didn't think that effective vaccines could appear in a fraction of the time taken for previous efforts.
Despite the vaccine's success, there was still plenty more to be thrown at us by viral evolution. The onslaught of highly immune-evasive variant was unforeseen for most of us. The coronaviruses family is less error-prone and more stable than many viruses. In the heat of battle, we had never before had to change the way we develop vaccines.
The real-life state of play today is not optimal. The vaccines rapidly induce high levels of protective, neutralising antibodies in most people, but these levels decline within months of each sequential dose. Omicron and the subvariant BA.2 have been able to modify almost all of the protective antibodies. As of late last week, there were more than 300,000 new cases a day in the UK, with hospital admissions and excess deaths holding steady at a new high. One of the highest vaccination rates in the world was not spared.
We are living in a precarious truce to keep the viral caseload manageable. There are signs that this isn't sustainable and that a strategy consisting of boosters in perpetuity may not be fit for purpose. There have been recent case Surges in Hong Kong, Denmark and Scotland. The effectiveness of later jabs can be altered by encounters with different vaccine types, according to new evidence. Booster performance could be less effective in the future.
The Wuhan strain is the single variant of sars-coV-2. We are in a world where no two people have the same exposure history, and we have never been exposed to the same diseases. Each of us has a unique immune memory.
Imagine a huge jar of pills of different colors, each good for responding to a given present or future variant. A person who has had an Alpha infection may have built up lots of green pills at the expense of others. If the next variant only needs yellow pills, this is not good for you. The order and type of exposure can affect how our immune system responds.
In a recent paper published in the journal Science, we compared the protective immunity of people who were in the first wave with those who were in the second wave. In second wave-infected people, encounters with an Alpha infection plus two vaccine doses gave lower protective (known as neutralising) antibody responses against the Wuhan andBeta variant, yet higher responses against Delta. The number of vaccines and strains will affect how our immunity holds up in the future. It needs more investigation.
These are complex problems requiring careful research, long-term planning, trials and even some intelligent crystal ball-gazing. We have to evaluate many approaches. Some places have announced a fourth dose roll out for first generation Pfizer vaccines, which cross-neutralises recent variants, but very suboptimally; some vaccine makers have pivoted to targeting the Omicron spike; others are working on polyvalent vaccines to include several different versions of spike, or clever
How should the world respond to a new disease?
This latter approach is exciting and the subject of recent efforts across many teams. There are advanced programmes that could be used to achieve local immunity and vaccine platforms that could be more durable.
The take- home message is that the pandemic is evolving with us and that there is a long, bumpy road ahead. The option to sleepwalk through this, taking automatic-pilot choices based on what was good enough in the first wave, is one we adopt at our peril. We have to look at options besides boosting through waves. This should be an urgent priority at a time when the US has cut vaccine research funding and the UK needs to maintain its momentum.
Danny Altmann is a professor of immunology at Imperial College London, who has contributed advice to the Cabinet Office, APPG on long Covid, and the EU.
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