Third shot's the charm? It's not clear with Covid-19 vaccines

A growing number of countries are considering third vaccine shots, but it is still not clear that this is the most effective way to tackle Covid-19 as new variants spread and it remains unknown how long their protection lasts.

Scientists say this is a complicated question and the answers could vary according to individual or national circumstances – or the vaccines involved.

The World Health Organisation says so far there is no evidence booster shots are needed.

“Currently, data shows us that vaccination offers long-lasting immunity against severe and deadly Covid-19,” WHO chief Tedros Adhanom Ghebreyesus said Monday (July 12).

“The priority now must be to vaccinate those who have received no doses and protection,” he said, in an apparent criticism of highly vaccinated nations planning extra shots amid an ongoing global shortage.

The United States has already booked 200 million doses of the Moderna vaccine, eyeing a potential need for boosters, while on Sunday (July 11) Israel began offering third shots to those with immune deficiencies.

Britain is preparing a possible roll-out of third doses for the elderly in September, while China is also evaluating whether they should be added to the current regime.

In Indonesia, which has struggled to access vaccines for its population of 270 million, the government has promised to give a third dose of Moderna’s vaccine to health care workers, who have largely been given two doses from Beijing-based Sinovac.

Dicky Budiman, an epidemiologist at Australia’s Griffith University, said Indonesia was in a “different situation” to developed countries, as doctors and nurses were being infected as they battled a surge of cases in a country where most people have not been vaccinated.

“They want to protect their health care workers … there’s no need to wait,” he said, adding that the infections in this high-risk group could indicate vaccine protection was either waning over time or had been reduced by the predominance of the Delta variant.

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If vaccine protection is falling over time, a booster shot could give the immune system a refresher on how to protect the body.

This is the case for a number of vaccines, such as the one for tetanus and diphtheria, where a booster is typically recommended every 10 years.

Viruses can also mutate to dodge immune protections, which could mean vaccines have to be modified to combat the new variants, as is the case with flu.

Understanding the extent to which these factors have an effect on Covid-19 vaccines will be key to deciding when or whether to use booster shots.

“If a vaccine started at 90 per cent effective, 10 per cent of people weren’t protected, so you follow that over time. (Later) you may find 20 per cent who are vaccinated are no longer protected and then 30 per cent,” said vaccinologist Nikolai Petrovsky, a professor at Flinders University in Australia.

“As you see that number with breakthrough infections increasing, you know the vaccine effect must be wearing off and you would then make a decision to revaccinate.”

Ashley St John, an immunologist at Duke-NUS Medical School, said most of the data that has been released suggests that immunity will be long-lasting for these vaccines, but it was appropriate to prepare for the potential need.

As for the impact of variants, while flu vaccines can need annual updates, she said there is not “the same speed of change” with the virus that causes Covid-19.

“Right now, we have too many new variants developing because we have such high levels of circulating virus. We need to reduce the infection burden, which would also limit new variants emerging,” said St John.

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One way to do that is to reduce the spread of the disease, which has prompted pleas for richer nations to stop hoarding supplies.

“Sharing vaccines is not only the right thing for others but selfishly it keeps us safe too,” said Sheena Cruickshank, an immunologist and professor at the University of Manchester in Britain.

The available data suggests vaccines have largely remained effective against severe disease caused by the variants, including the highly transmissible Delta variant that the WHO expects will become dominant globally.

However data for Sinovac and Sinopharm’s vaccines is not yet available.

But concerns about declining antibody levels and variants that are less sensitive to antibodies generated through natural infection or vaccination was “driving the thinking” around booster shots, especially for vulnerable people, according to Jonathan Ball, a professor of molecular virology at the University of Nottingham in Britain.

Pfizer’s chief scientific officer Mikael Dolsten told Associated Press that a recently reported drop in the Pfizer/BioNTech vaccine’s effectiveness in Israel could be due to waning antibodies in people vaccinated at the start of the year, rather than reduced ability against the Delta variant spreading there.

The company has signalled it plans to apply for authorisation for a third dose in the United States, after initial data suggested it could prompt a five to tenfold increase in antibody levels several months after the initial shots.

The US drug regulator said Americans do not currently need boosters.

Other companies have suggested similar results have been recorded.

Last month Sinovac chief executive Yin Weidong told China Central Television that clinical trial volunteers who received a third Sinovac shot after three and six months saw a tenfold increase in antibodies after a week.

A third dose of the AstraZeneca shot given at least six months after a second dose, boosted antibody levels six folds and resulted in higher neutralising activity against the Delta variant, the company said last month.

Some countries have already moved to provide boosters following concerns about waning antibodies. The authorities in Bahrain and United Arab Emirates are already offering third shots of Sinopharm or Pfizer/BioNTech to those given the Sinopharm vaccine six months ago.

In Thailand and Turkey, which relied on Sinovac for their early roll-outs, the authorities decided to give health care workers booster doses of various vaccines. Thailand, like Indonesia, has reported hundreds of infections in vaccinated health workers.

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In Turkey, recent research involving 1,053 Turkish health care workers found that 95 per cent saw reduced levels of antibodies three months after vaccination, while 23 per cent had antibody levels below the threshold researchers classified as effective.

Erhan Eser, a professor at Turkey’s Manisa Celal Bayar University School of Medicine, who was involved in the research, cautioned that real-world indicators are more important and said the Turkish decision about boosters was also based on concerns about the Delta variant.

Petrovsky, from Flinders University, said a drop in antibodies is not proof the original vaccine is no longer working. Instead, measuring real vaccination outcomes – such as the number of breakthrough hospitalisations – would be key.

“We shouldn’t be embarking on a widespread campaign of third doses of the same vaccines without strong evidence as this will divert valuable supplies from the developing world,” he said.

This article was first published in South China Morning Post.