isn the summer, Israel began offering third doses of the Pfizer / BioNTech vaccine to those over 60 years of age. It was the first country to start giving “booster shots” to people vaccinated at least five months previously. Prime Minister Naftali Bennett announced the decision after a study by Leumit Health Services, an Israeli healthcare provider, showed that people over 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 August 29, Israel began offering a third dose to anyone aged 12 and over, who had waited for this period. The question for other countries now is whether to follow Israel’s example.
The first data assessing the early impact of the third dose program was published last week in the New England Journal of Medicine (NEJM). It showed that two weeks after more than 1.1 million over 60s received their third dose, they were 11.3 times less likely to be infected with the unusually contagious Delta variant that is currently prevalent in Israel and the rest of the world. the world.
In other words, the third doses are very effective in preventing people from getting infected with Delta, among those who are ready to be vaccinated. When the third doses significantly reduce a person’s susceptibility to infection, it creates a barrier to the transmission and spread of the virus. This is important because an increasing number of people are infected despite their vaccination (although the risks of infection, spread and serious illness remain greatest in unvaccinated people). And they have similar peak levels of the virus in their noses as those who are unvaccinated, contributing to the relentless spread of the virus.
The third doses stimulate the production of neutralizing antibodies which are both stronger and more extensive against the viral variants than those caused by a second dose. Taken together, the booster shots aren’t just an immune refresh – they are an immunologic upgrade. These superior neutralizing antibody responses create an immunological buffer that is effective even against the Sars-CoV-2 Delta variant, explaining the dramatic reduction in the risk of infection after the third doses in Israel. The same buffer would be expected to reduce the need for frequent “stimulation” in the future, as higher levels of neutralizing antibodies are expected to confer longer lasting immunity.
Other countries have been watching Israeli data closely, but have been reluctant to adopt universal third doses for young people for two main reasons. First, current vaccination programs outside of Israel continue to protect against serious illness, hospitalization 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 hospitalizations in many places in the United States, despite widely available vaccinations, exposes the limitations of its use as a single benchmark.
Another reasonable standard for evaluating the impact of the vaccine is the prevention of infections, even clinically mild ones, to minimize transmission within communities. The status quo of vaccinated individuals who are not optimally protected against infection and transmission, large populations (e.g. young children) who are not allowed to be vaccinated, and large numbers of unvaccinated individuals allowed Delta infections to rage.
Dramatically reducing the number of infections among people who have been vaccinated three times, one of the main findings of the NEJM article, is rapidly reducing the number of susceptible individuals able to maintain the continued spread of the virus. Israel is already providing a real-world test of the concept, and the recent decline in its new cases is encouraging. Of course, such programs must exist alongside efforts to immunize unvaccinated people who are most at risk. Persuading unvaccinated people has been difficult, even with financial incentives and other creative strategies. Meanwhile, there is a significant segment of the population that would enthusiastically demand third doses as soon as they become available. Implementing third-dose programs would bring immediate benefit directly to this highly motivated group and the communities in which they live, while programs to encourage unvaccinated people to get vaccinated continue.
Second, there is an understandable concern that programs like Israel’s perpetuate inequalities. More vaccines are definitely needed for more people in more places. This alone should not preclude considering third-dose programs in vaccine-experienced countries struggling with Delta outbreaks. While the breathtaking short-term protection seen in clinical trials initially supported a two-dose vaccine series, the most recent data suggest that a primary vaccination 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 doses of vaccine to minimize the threat of Covid-19 globally should be a clear call to immediately invest in sustainable vaccination programs around the world. Creating and maintaining the infrastructure for sustainable programs would likely have the side effect of improving access to other essential vaccines that are not yet universally available. For example, less than 75% of infants in Africa receive all three doses of the hepatitis B vaccine. There is a precedent for such massive and transformational infrastructure investments that benefit public health: UNAids estimates that more than 70 % of people living with HIV now have sustainable access to antiretroviral drugs.
Faced with a potentially difficult winter, countries with already a vaccine supply are at a crossroads. There is a tendency to look askance at the data that has been collected in other countries with subtly different demographics and Covid-19 epidemics. The Israeli experience is not perfectly aligned with that of other countries that use several different types of vaccines, with different vaccination schedules, have varying demographics, socio-economic conditions and Covid-19 burdens. The biology of immunity to Sars-CoV-2, however, is the same whether you are in Tel Aviv, Tokyo, or Toronto. Israel’s pioneering work of making third doses the standard provides an instructive model for other countries to follow as quickly as possible, while ensuring that it becomes the global immunization standard for everyone, no matter where they live. .