Up To 300% More Antibodies When Second Dose Delayed: Study

Faced with a limited supply of shots and anxious populations waiting their turn, more countries are turning to an initially controversial strategy that’s now been vindicated by scientific studies: doubling or tripling the intervals between the first and second Covid vaccine dose.

A delay in getting the second shot not only allows the existing supply of shots to be more widely distributed, it boosts their protective power by giving the immune system more time to respond to the first inoculation. Levels of antibodies produced to fight off the virus are 20% to 300% higher when the follow-up vaccine comes later, new research shows.

That’s welcome news for places like Singapore, which is grappling with a rare, albeit small, rise in cases after strict mitigation measures contained the virus last year. The city-state is now extending dose intervals — previously three to four weeks — to six to eight weeks, in order to reach a goal of covering its entire adult population with at least one shot by the end of August. India, facing a catastrophic outbreak, is advising 12 to 16 weeks between shots.

Other nations in similar straits – with few vaccine doses and antsy populations – are likely to follow.

“If I could, I would push a button that says right now, this second, we give one dose to everybody we can reach,” Gregory Poland, a virologist and director of the Mayo Clinic’s Vaccine Research Group. “We’ll get around to second doses later.”

“In the midst of a world on fire, you put out as many fires as you can, as quickly as you can,” Poland said.

The reassuring evidence on longer dosing intervals wasn’t available when the vaccine rollout first started at the end of 2020. Then, countries limited their use to the highest-risk people and guaranteed a second shot was waiting for those segments. The U.K. was the first to abandon those constraints amid a massive outbreak in late 2020 – a move that was initially criticized but has now proved prescient.

More Powerful

The research suggests that the first shot primes the immune system, allowing it to start making protective antibodies against the virus. The longer that response is allowed to mature, the better the reaction to the second booster shot that comes weeks or months later.

The benefits from longer dose intervals is being seen across all types of vaccines.

People over 80 given a powerful mRNA vaccine from Pfizer Inc. and BioNTech SE had an antibody response that was 3.5-fold higher if the second shot came after three months, rather than three weeks. Other studies concluded that delaying the final shot for nine to 15 weeks averted more hospitalizations, infections and deaths, while one from Canada suggested the biggest benefit came from a six month delay.

There are drawbacks. The additional time between doses means it will take longer for countries to protect their populations. While one shot offers some level of benefit, people aren’t considered fully immunized until several weeks after their second dose.

The interval is particularly dangerous when less potent vaccines are being used or more transmissible variants of the virus are circulating.

Some countries are pushing the boundaries. India’s delay of three to four months between doses, among the longest in the world, means those scrambling to get vaccinated amid its current outbreak won’t be fully protected until the summer or the fall.

While studies suggest the optimal spacing between AstraZeneca shots is 12 weeks, there is scant data on the impact of stretching that to 16 weeks. The British drugmaker’s shot accounts for the majority of inoculations in India now.

The greater delay can also increase the logistical hurdles involved in getting millions of people to return to complete the series, especially if they feel they already have some coverage from the first shot. It’s already difficult to get people in developing countries to return given transportation and communication challenges.

“When you have any kind of a two-dose schedule, it’s hard logistically,” said Gigi Gronvall, a senior scholar at the Center for Health Security at the Johns Hopkins Bloomberg School of Public Health. “You worry about when people will come back for a second shot, or if you will lose them entirely.”

It’s a tradeoff many places are willing to make, particularly given the limits on vaccine availability. With a new variant first identified in India already spreading in Singapore, officials want to administer a first dose to about 4.7 million people by the end of the summer.

“We’re vaccinating 40,000 people a day at the moment, so you can do the math and work out how long that’ll last,” said Dale Fisher, an infectious diseases professor at the National University of Singapore. “And that’s a fairly rigid pipeline. It’s not like you can just order more.”

By delaying the second dose, several hundred thousand people will get their first injection sooner, he said.

“We’re comfortable that there’s no downside to this.”