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Does splitting a vaccine dose reduce its efficacy?

As governments aim to stretch their supplies of the covid-19 vaccine, they’re proposing ideas such as a smaller dose or delayed second shot. Scientists are not amused.

A healthcare worker prepares to receive her second round of the covid-19 vaccine in Florida, US.
A healthcare worker prepares to receive her second round of the covid-19 vaccine in Florida, US. (AP)

Governments in a number of countries, including UK and US, are looking for ways to stretch their supply of the covid-19 vaccine as production is taking longer than expected. In India, there’s a debate over the speed with which two vaccines have been approved, although with restrictions. Greenlighting Bharat Biotech’s Covaxine, in particular, has come under criticism as the results of the phase 3 trials to determine efficacy are still not out.

In other countries, the debate is about proposals to space out two-dose vaccines (such as the University of Oxford and AstraZeneca vaccine, which Serum Institute of India is manufacturing) by delaying the second shot, or reducing the size of the dose to be administered.

The real issue that concerns scientists and experts is that none of these vaccines—whether AstraZeneca, Pfizer or Moderna—have been tested in rigorous trials and the rollout is being done on the basis of limited evidence. In such a situation, halving or delaying doses may not be ideal. The other concern is a practical one: People may not return for the second dose and health authorities will find it harder to track those who have been vaccinated.

In the UK, the government has already chosen to provide the second shot after 12 weeks, instead of three-four weeks, so that more people can be covered in the initial stages. Maximising the number of people who have partial immunity “should reduce the number of severe covid-19 cases and thus alleviate the burden on hospitals”, Michael Head, a global health expert at University of Southampton, UK, told Reuters.

There is no long-term evidence that any of these vaccines will offer lasting immunity based on just one dose, or how effective they will be if the second dose is delayed, reports Reuters. BioNTech and Pfizer have warned that they had no evidence their vaccine would continue to be protective if the second dose was given more than 21 days after the first. The World Health Organisation has recommended that people should get two doses of the Pfizer and BioNTech vaccine within 21-28 days.

Faced with the challenge of giving a larger number of people a shot in the arm, conflicting statements are also emerging from experts. The US’ leading infectious disease expert Dr. Anthony Fauci told CNN last week, “I would not be in favour of that,” when asked whether the dose could be halved or reduced. “We’re going to keep doing what we’re doing,” he added. A few days later, The New York Times reports, Moncef Slaoui, scientific adviser of US’ Operation Warp Speed for vaccine development and distribution, suggested “giving some Americans two half-doses of the Moderna vaccine” for people aged 18 to 55, saying there was some clinical trial data to back this approach.

Several other scientists said the data is still “very fuzzy”. Pharma company leaders too seem unwilling to back a reduced or delayed dose. Moderna CEO Stephane Bancel said that data available from trials on the efficacy of a half-dose version of their vaccine is unlikely to convince regulators to approve such a strategy. “That data has not been published yet. It will be soon,” Bancel said at a Goldman Sachs event. “I don’t see a world where that data is enough to convince the medical community.”

Ideally, “it is safest and most cautious” to use vaccines in conditions exactly matching those of their trials, Stephen Evans, professor at the London School of Hygiene & Tropical Medicine told Reuters. However, “in the real world, this is never so”, he said.

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