In the summer, Israel began offering third doses of the Pfizer/BioNTech vaccine to the over-60s. It was the first country to start administering “booster shots”, to people vaccinated at least five months previously. The prime minister, Naftali Bennett, announced the decision after a study by Leumit Health Services, an Israeli healthcare provider, showed that those over the age of 60 who had been vaccinated more than five months previously were three times more likely to be infected than those vaccinated more recently. As of 29 August, Israel began offering a third dose to everyone aged 12 and older, who had waited this period of time. The question for other countries is now whether to follow Israel’s lead.
The first data evaluating the early impact of the third dose programme were published last week in the New England Journal of Medicine (NEJM). It showed that two weeks after more than 1.1 million over-60s had received their third dose, they were 11.3 times less likely to become infected with the exceptionally contagious Delta variant that currently predominates in Israel and across the world.
In other words, third doses are highly effective at preventing people from becoming infected with Delta, among those who are willing to be vaccinated. When third doses dramatically reduce a person’s susceptibility to infection, it creates a barrier to the onward transmission and spread of the virus. This is important because growing numbers of people are getting infected despite being vaccinated (though the risks of infection, spread and severe illness remain greatest among those who are unvaccinated). And they have similar peak levels of virus in their noses to those who are unvaccinated, contributing to the unrelenting spread of the virus.
Third doses stimulate the production of neutralising antibodies that are both higher in magnitude and have greater breadth against viral variants than those elicited by a second dose. Taken together, booster jabs aren’t just an immune refresher – they are an immunological upgrade. These superior neutralising antibody responses create an immunological buffer that is effective even against the Sars-CoV-2 Delta variant, explaining the dramatic reduction in risk of infection following third doses in Israel. The same buffer would be expected to reduce the need for frequent “boosting” in the future, as higher levels of neutralising antibodies are predicted to confer longer-lasting immunity.
Other countries have watched the Israeli data closely but have been reluctant to embrace universal third doses for younger people for two main reasons. First, current vaccine programmes outside Israel continue to protect from severe disease, hospitalisation and death. This is a reasonable standard for evaluating vaccine protection, but it is not the only one. The crippling impact of Delta variant infections on hospitalisations in many locations in the US, despite widely available vaccinations, exposes the limits of using this as the sole benchmark.
An alternative reasonable standard for assessing vaccine impact is the prevention of even clinically mild infections in order to minimise transmission within communities. The status quo of vaccinated individuals who are not optimally protected from infection and transmission, sizeable populations (eg, young children) who are not allowed to be vaccinated, and large numbers of unvaccinated individuals have allowed Delta infections to rage.
Dramatically lowering the number of infections among people who have been vaccinated three times, one of the key outcomes of the NEJM paper, quickly reduces the number of susceptible individuals who are able to sustain the virus’s continued spread. Israel is already providing a real-world test of this concept, and the recent decline in its new cases is encouraging. Of course, such programmes need to exist alongside efforts to immunise those unvaccinated who are at the highest risk. Persuading unvaccinated people has been difficult, even with financial incentives and other creative strategies. Meanwhile, there is a sizeable segment of the population who would enthusiastically clamour for third doses as soon as they become available. Implementing third-dose programmes would provide an immediate benefit directly to this highly motivated group and the communities in which they live, while programmes aimed to encourage unvaccinated people to be immunised continue.
Second, there is an understandable worry that programmes such as Israel’s perpetuate inequality. More vaccines are undoubtedly needed for more people in more places. This alone should not preclude consideration of third-dose programmes in vaccine-experienced countries struggling with Delta outbreaks. While the breathtaking short-term protection observed in clinical trials initially supported a two-dose vaccine series, the newer data suggests that a primary immunisation series followed by an additional dose months later should be the new standard protocol. This is already the schedule for other viral vaccines, such as the hepatitis B vaccine.
This does not mean that the needs of the rest of the world should be ignored. Indeed, the potential need for three vaccine doses to minimise the threat of Covid-19 globally should be a clarion call to invest immediately in sustainable immunisation programmes worldwide. Creating and maintaining the infrastructure for sustainable programmes would likely have the side-effect of improving access to other critical vaccines that are also not yet universally available. For example, less than 75% of infants in Africa receive all three doses of the hepatitis B vaccine. There is precedent for such massive, transformational infrastructure investments that benefit public health: UNAids estimates that more than 70% of those with HIV now have sustainable access to antiretroviral drugs.
Facing a potentially difficult winter, countries with an existing vaccine supply are at a crossroads. There is a tendency to look askance at data that was collected in other countries whose demographics and Covid-19 epidemics are subtly different. The Israeli experience is not perfectly aligned with other countries that use multiple different vaccine types, with different timing of vaccination, have varying population demographics, socioeconomic conditions, and Covid-19 burdens. The biology of Sars-CoV-2 immunity, however, is the same whether you’re in Tel Aviv, Tokyo or Toronto. The pioneering Israeli work of making third doses the standard provides an instructive template for other countries to follow as quickly as possible, while also ensuring that this becomes the global standard of vaccination for everyone, no matter where they live.