The rapid development and rollout of effective vaccines have been game changers in the fight against Covid-19, allowing the world to begin to see a pathway out of the pandemic. But these shots don’t offer unlimited protection and may not be as effective against emerging variants. This is where booster shots come in.

With Pfizer Inc. and other drugmakers running trials now to assess how long vaccine protection lasts and when boosters might be needed, Sam Fazeli, a Bloomberg Opinion contributor who covers the pharmaceutical industry for Bloomberg Intelligence, answers questions about what we know now.  The conversation has been edited and condensed.

What is a booster shot? Why might we need one?

Vaccine boosters give the immune system another “kick” to raise a response to a pathogen. They are used when we are worried about the level of protection an initial course of vaccination confers. In the case of Covid-19 vaccines, the need may arise because vaccine-induced immunity has waned or a variant has arisen that is less responsive to antibodies produced by vaccination. 

What will determine whether we need one?

The worst way to determine when boosters are needed would be to wait for infection rates to rise in vaccinated people. It would be the simplest way, of course, but it would be a bit late by then and thus not the best approach from a public health perspective. We’re seeing this happen now in the United Arab Emirates, where China’s Sinopharm shot was used. The infection level is rising despite a high degree of supposedly full vaccination, which suggests the possible need for a booster. The better way to do it would be to follow a cohort of vaccinated people of various ages, ethnicities and health conditions and conduct regular blood antibody analysis looking for neutralizing antibody levels to whatever variants are circulating around the world. But even better than that would be to not wait for any data and just give people a booster shot while we assess vaccines’ ability to neutralize variants. This is costly but likely the most effective way to reduce the public-health and economic impact. 

What kind of boosters are in development? Will it be a similar dose as say a single shot of the double-shot vaccines?

A lot of this is still being worked out. But Pfizer has decided, based on some clinical trial and real-world data of the shot it developed with BioNTech SE, to use the same dose it now offers, BNT161b2, though it is still planning to develop vaccines that target variants. Moderna Inc. is aiming to be ready with three different approaches: one using its current vaccine (mRNA-1273), another that channels the B.1.351 variant of the virus first found in South Africa (mRNA-1273-351), and yet another approach that combines the two.

Covid vaccines have been free to consumers and relatively inexpensive to governments. Is that likely to be different for boosters, especially because there seems to be less government funding?

It’s possible, and I think it will depend on volume. So if a country decides to buy only a small number of doses to provide boosters to its elderly population, who are most at risk of losing protective immunity, then the price is likely to be higher than a country that is buying for its whole population.

What are the benefits or problems of tailoring shots to variants rather than giving another dose of the original?

The benefit has been shown by Moderna. Their mRNA-1273-351 not only boosted the immune response against the original “Wuhan” version of the virus, as measured by neutralizing antibody levels, but was also much more effective in neutralizing the B.1.351 variant. The downside is that variants constantly evolve with many different mutations. For example, the B.1.617 variant first described in India now represents three different variants, with B.1.617.2 spreading in the U.K. This begs the question of which variant we might need to address most with a new booster.

How can you study boosters? Do you need to do another big trial, or are there shortcuts?

No – this is relatively easy. It’s a small trial, involving people from a variety of demographics. You gauge their ability to neutralize whichever virus you’re interested in before a booster and then seven to 14 days after receiving one by measuring antibody levels. There is increasing evidence that this measure is the best indicator of protection against an infection.

Could boosters protect against multiple variants?

Sure. As mentioned, Moderna is working on exactly that. The question is how many variants should be targeted in a vaccine and whether there is a limit to that as regards the particular vaccine technology. We don’t yet know the limit when it comes to messenger RNA (mRNA) vaccines such as Pfizer-BioNTech’s and Moderna’s, but we do know that protein-based vaccines, such as those being developed by Novavax Inc. and Sanfoi-GlaxoSmithKline Plc, can theoretically cover many variants. For example, Sanofi’s Hexaxim vaccine targets diphtheria, tetanus, pertussis, hepatitis B, polio and Haemophilus influenza type B, though they are not all protein-based.

Can vaccines that haven't been approved yet in any form play a role as boosters?

I don’t think so, unless there is a scientific reason to use them. This would include potential for a better immune boost if a different vaccine is used. It may also be desirable to use a killed-virus vaccine for better coverage against disease given these vaccines use the entire virus to build protection rather than just the spike protein, like many in use now.

What about mixing vaccines — for instance, giving Pfizer or Moderna boosters for people who received  Johnson & Johnson  and AstraZeneca Plc shots? Could it be good to mix vaccines?

This is actually being studied in the U.K. with the Pfizer-BioNTech and AstraZeneca vaccines. So far we don’t know what the impact on immune response is, though it should be at least as good with a “heterologous prime-boost” approach, as it is referred to when you use two different vaccines for the first and second shot. It’s also already recommended that those who have an allergic reaction to the mRNA vaccines be given adenovirus vaccines, such as Astra or J&J, as a second shot. As for the third booster, again we don’t have data, but I would be surprised if it would be a problem. Also, I would suggest we do not use J&J or the Astra vaccine after we have cases under control as there is the risk of serious blood clots.

Is it even ethical to give boosters in some countries like the U.S. and U.K. when so much of the world hasn't even received one shot?

This is a very tough subject. You can also ask whether it’s ethical to be vaccinating adolescents or children before the much more vulnerable population in lower-income countries have had a single shot. At the end of the day, the more a country’s population is vaccinated, the better its chances of fighting off the next wave of infections, whether this is achieved by vaccinating children or boosting older individuals. But people who live in an area with a high vaccination rate and low cases are arguably less needy than those living where cases remain high and many haven’t even had round one of shots. And when many parts of the world are unvaccinated or only partly inoculated, there’s a greater risk of a variant evolving that can evade vaccines and threaten everyone. As I said, it’s difficult.