Switzerland is now offering a Covid-19 booster shot to to the 65+ and at-risk who has had their two Covid-19 vaccinations at least six months ago. It may soon be extended to all adults. I had my third shot last Thursday with no side effects (not even a localized sore spot) and was surprised to receive a Pfizer booster after being fully vaccinated earlier this year with the Moderna vaccine. The mRNA in both vaccines encode the same S-2P protein which differs from the covid19 spike protein by two amino acids only. These stabilize the spike protein so that it can train the immune system before it enters the host cell (see here for details).

However, they differ in the “packaging” regions around the actual genetic code for the protein. These leader and trailer regions are responsible for initiating and regulating the translation of the mRNA to produce the protein which stimulates an immune response. The other major difference between the two vaccines is that there is a much larger dose of vaccine (100 mg) in a Moderna dose compared to a Pfizer dose (30 mg). While the initial protectiveness of both vaccines is similar at around 94-95%, there is some evidence that the protectiveness may decline at a somewhat slower rate for Moderna than Pfizer.

There is also evidence that getting a different booster shot that the vaccine you originally received actually enhances the immune response more than getting the same type of vaccine for a third dose (see here and here). There is a small advantage mixing the two mRNA vaccines (Pfizer and Moderna) as I have done,  and a substantially enhanced immunogenicity when non-RNA vaccines (eg. Astrozenica or Johnson and Johnson).

So how effective is the booster shot? A large study published in the New England Journal of Medicine in October compared outcomes in 1.14 million Israeli adults aged 60 years and over who had received two Pfizer doses at least 5 months earlier, of whom around half received a Pfizer booster shot and the other half did not. The analysis controlled for possible confounding factors including age, sex, demographic group and the date of the second vaccine (to ensure there were not differences in the time since second vaccine between the control and booster group).

The results were dramatic. At least 12 days after the booster dose, the rate of confirmed infection was lower in the booster group than in the nonbooster group by a factor of 11.3; the rate of severe illness was lower by a factor of 19.5. These findings clearly show the effectiveness of a booster dose even against the currently dominant delta virus. Recent reports have suggested that the efficacy of a vaccine administered 6 months earlier  against the currently dominant delta virus is reduced by approximately 50% compared to the post-vaccination efficiency of 95% against the alpha variant (see here, here and here). So the susceptibility to the delta variant of a person who has received the third dose would be reduced from around 50% to 5%, and even less if they receive a different vaccine than their first two shots.

On July 30, 2021, Israel was the first country in the world to make available a third dose of the BNT162b2 vaccine against Covid-19 to all persons who were 60 years of age or older and who had been vaccinated at least 5 months earlier. Since then, Israel has extended the booster program to the entire population. The following graph shows trends in vaccination rates and booster doses for Israel and Austria (as a typical example of a Western European country). The fully vaccinated rate (two doses) is essentially identical for the two countries from August onwards at a little over 60%. Booster doses per 100 people rose from zero at the end of July to over 40 per 100 currently.

The next graph shows the daily new cases per million for Israel and Austria (which is currently experiencing one of the largest increases in Delta cases in western Europe).  Israel had a huge spike in infections this summer due to the highly infectious Delta strain, together with a combination of waning immunity five or six months after the second jab. Its clear that the booster shots were definitely a game changer.  Over time, there was a very steep reduction in infections, hospitalizations and deaths among the people that got the booster shot. Israel went from over 11,000 new cases a day at the peak, down to a few dozen today. Before the booster campaign started hospitalizations were rising among vaccinated people whose immunity had waned, but the overwhelming majority of hospitalizations now are of people who are unvaccinated.

The same combination of waning immunity and Delta are now causing rising cases in Europe, as illiustrated in the following plot. Austria, Belgium and the Netherlands are currently the hardest hit (see graph below), with average daily new cases well over 1,000 per million, higher than any previous wave. In most of the countries on this graph, fully vaccinated rates are somewhere between 60 and 75%. That means around 25 to 40 percent of these populations are unvaccinated and their much higher susceptibility to infection is driving the latest surge in Delta infections.

Germany, Austria and the German-speaking region of Switzerland have the largest shares of unvaccinated populations in all of Western Europe. About one in four people over 12 is unvaccinated, compared with about one in 10 in France and Italy, and almost none in Portugal.

Governments are struggling to address this shortfall in vaccination levels. Austria has introduced a lockdown for anyone over the age of 12 who is not vaccinated and foreshadowed compulsory vaccination for all adults. Germany is considering new restrictions and in Saxony the unvaccinated are already barred from non-essential shops and other locations. The Netherlands has flagged that they will move to full lockdown for the unvaccinated but not the vaccinated. Switzerland has a referendum next weekend on whether to continue with the vaccine mandate which allows only fully vaccinated people to go to theatres, restaurants, gyms and other indoor public venues.