Since early 2020, the tragic reality of the pandemic has unfolded, killing millions, disrupting normal social interactions, destabilising economies and plunging the world into uncertainty. Between 4.3 and 11.6 million people have died. Amid this deepening gloom, vaccines have brought hope. Their development is a triumph of science; the manufacture and deployment of 4.4bn doses by a handful of developers is astonishing, joyous. In the UK alone, 87m doses have been administered, saving more than 84,000 lives. Globally, the number of lives saved by vaccines is expected to be in the millions. So why is there still so much suffering around the world? Thousands of people are still dying of Covid every week. Hospitals are overwhelmed and many countries are in despair, urgently pleading for vaccines because they have virtually none. We are in this position simply because the doses we have are not being distributed first to those who are at highest risk of getting seriously ill or worse yet, dying. The vast majority of people who will die of Covid this year could have been saved if we had got this right. Vaccinating those at risk everywhere is in our self-interest. It may reduce the risk of new variants arising, and will relieve pressure on health systems, open travel, resuscitate the global economy, and raise the international authority of politicians prepared to take such moral leadership. Despite the reality that a million more people are expected to die of Covid across the world by December, and many more live in fear with no chance of getting vaccinated, governments in the west are now considering giving a third booster dose of vaccine to those who have already received two. In a time of great global human need, we need to clearly outline a strong scientific case for giving booster shots. And we must get the timing right; if some need a boost, this must not deny a lifesaving vaccine to those who should be at the top of the list. The scientific and public health case for large-scale boosting is incomplete and not clear. People experience a fall in antibody levels over time after vaccination, and we know from several studies that a booster will reverse this decline. If really high levels of antibodies are better at preventing minor infection, perhaps there is a case for boosters after all. But the focus of vaccination policy cannot be on sustaining very high levels of antibodies to prevent mild infection. If we focus on antibody levels alone, we could end up vaccinating everyone repeatedly to cope with a virus that keeps mutating. The point of vaccination isn’t to prevent people from getting mild infections; it’s to prevent hospitalisation and death. As we see in the daily case numbers, the virus that causes Covid can still infect vaccinated people. Cyclically infecting immune individuals is fundamental to the biology of human coronaviruses. This is not in itself a cause for alarm. The vaccines are still providing high levels of protection against severe disease. Our immune systems have been trained by vaccines to respond when exposed to the virus, even if antibody levels have fallen. So instead of being concerned about whether people will be infected, we should be concerned about whether that infection could lead to serious disease, hospital admission, or worse. The information we need – which we don’t yet have – is the level of antibody or T-cells required to prevent people from getting seriously ill. If this could be measured, and we saw protection dropping towards that level, there would be a clear case for administering booster shots. But we can’t measure this yet. And at the same time, high-risk groups around the world are still awaiting their first shots. All we can do is analyse the clinical data to see when or if there is a point where boosting becomes necessary. This is being watched carefully and closely by public health authorities and the World Health Organization. It will become clear one way or the other, and policy will rightly evolve in response. For now, we are in unknown territory. We might need to give people booster shots to increase and extend immunity, but we might not. There is precedent in both directions. Just one dose of yellow fever vaccine provides lifelong protection. Conversely, we use five to six doses of tetanus vaccine for lifelong protection, and the flu vaccine is given annually. Where will Covid vaccines sit? It is highly unlikely that vaccine protection against severe disease will suddenly fall off a cliff and the ongoing pandemic will be catastrophically rebooted. Small mutations in the virus will occur to help it survive better in vaccinated populations. But those mutations don’t render our vaccine immunity impotent. We are still protected from severe disease caused by the main variants that have emerged. So far. This is not an all or nothing argument. We need ongoing careful analysis of the data to ensure there are no groups for whom boosters are already warranted. On the other hand, for those who don’t respond well to vaccines, more doses won’t help, and access to new treatments is urgently needed. This is a key moment for decision-makers. Large-scale boosting in one rich country would send a signal around the world that boosters are needed everywhere. This will suck many vaccine doses out of the system, and many more people will die because they never even had a chance to get a single dose. If millions are boosted in the absence of a strong scientific case, history will remember the moment at which political leaders decided to reject their responsibility to the rest of humanity in the greatest crisis of our lifetimes. Since we have the two-dose luxury of having time on our side, we should not rush into boosting millions of people, while time is running out for those who have nothing. First doses first. It’s that simple. Andrew Pollard is director of the Oxford Vaccine Group at the University of Oxford; Seth Berkley is the chief executive of Gavi, the Vaccine Alliance