Moderna study suggests half doses offer strong immune response, but experts caution against changing approach

There’s now early evidence showing Moderna’s coronavirus vaccine may elicit a strong immune response even through half doses, prompting hope that further research could back up the results and eventually allow countries like Canada to stretch out vaccine supplies.

The company’s peer-reviewed findings, based on a Phase 2 trial, were published online by the journal Vaccine last week.

The study looked at the mRNA vaccine’s “immunogenicity” — its ability to provoke an immune response — through both anti-virus, spike-binding antibody levels and neutralizing antibodies, which help to block reinfection.

Researchers determined within a two-dose regimen that both the current amount of vaccine dose and half that amount being given each time were capable of “significant” immune responses.

Those findings are welcome news, though not yet worth changing dosing approaches, said Dr. Zain Chagla, an infectious disease specialist and associate professor at McMaster University in Hamilton.

“But it does bring up the urgent need to do a Phase 3-type clinical trial of full dose versus half dose and see what happens,” he said. 

“The implications, obviously, are you all of a sudden double your vaccine supply overnight if this seems to work out.”

Boxes containing the Moderna COVID-19 vaccine are prepared to be shipped at a distribution centre in Olive Branch, Miss., in late December. (Paul Sancya/Reuters)

Immune response ‘increased substantially’

The Moderna vaccine is one of two options currently approved and being used in Canada to combat the spread of COVID-19, with more than 40 million doses ordered by the federal government.

Based on full clinical trial results, the current approach requires two doses of the vaccine, spaced 28 days apart.

The company’s recently released findings looked at both a full dose of 100 micrograms and a half dose of 50 micrograms, given as two doses in a randomized, observer-blind, placebo-controlled trial.

At eight different U.S. sites, a total of 600 participants were divided into age cohorts and randomly assigned at a 1:1:1 ratio to receive either the two full doses, two half doses, or two placebo doses.

By 28 days after the first shot, anti-virus spike-binding antibody levels and neutralizing antibodies were higher among people who’d been given the full dose compared to the half dose.

But that difference was “less apparent” after participants received both rounds, Moderna’s research team found.  

Both binding antibodies and neutralizing antibodies “increased substantially” by the two-week mark after participants were fully vaccinated and remained elevated through day 57, the researchers wrote.

A registered nurse draws up the Moderna COVID-19 vaccine into a syringe at a hospital in Brattleboro, Vt. The U.S. government helped fund the company’s most recently published research. (Kristopher Radder/The Brattleboro Reformer/The Associated Press)

Questions over duration of protection, variants

Outside experts who spoke to CBC News all stressed the need for future research before changing Canada’s dosing approach, given the short two-month time period and small, homogeneous group studied by Moderna. 

Chagla also said there’s a clear need to understand longer-term immunity and how other elements of the immune system — such as T-cells, which target specific bodily invaders — might be affected as well.

“The point nobody can answer for you is how long you will have protection,” said Horacio Bach, an adjunct professor in the division of infectious diseases at the University of British Columbia’s faculty of medicine.

“Nobody knows. Nobody can tell you. There are no studies; that’s the reason it’s a global emergency.”

Dr. Noni MacDonald, a researcher focused on vaccine safety who is also a professor at Dalhousie University’s department of pediatrics in Halifax, stressed that while Moderna’s study did show similar immunogenicity with two different concentrations of the vaccine, it was also based on “old data.”

The research was conducted between late May and early July 2020 — long before the clear rise of multiple virus variants, which may be more transmissible or capable of evading the body’s immune response.

If the findings hold up against emerging variants, it could mean countries like Canada could one day “stretch what we have” when it comes to Moderna shipments, MacDonald said in an email exchange with CBC News.

But right now, that’s not yet a possibility. Already the company says its vaccine may be less effective against the B1351 variant, requiring it to develop an alternative version for booster shots.

Immunologist and microbiologist Nikhil Thomas says it’s important to ‘suppress the spread of these variants,’ as the coronavirus variant first identified in the U.K. is replicating faster and transmitting ‘at a higher frequency.’ 4:17

U.S. officials discussed half-dosing

Despite limited data on the benefits of using half-doses, particularly against emerging variants, there has been discussion south of the border over taking that approach, with the U.S. government also helping fund Moderna’s most recently-published research.

In January, Moncef Slaoui, then-chief adviser of the former U.S. president Donald Trump administration’s vaccine effort — one dubbed Operation Warp Speed — said officials were considering giving half-doses of the Moderna vaccine to American adults under the age of 55.

The same month, the U.S. Food & Drug Administration released a statement shooting that idea down, saying any changes to dosing or schedules of approved vaccines would be “premature and not rooted solidly in the available evidence.”

On this side of the border, Health Canada officials told CBC News the agency has not received an application from Moderna to amend its vaccine authorization, but would “thoroughly review” one if it was submitted.

Canada has other vaccines in line for approval — how they compare to the ones already being rolled out and how COVID-19 variants are a complicating factor. 2:03

Dosing strategies have long-term impact

While Bach suspects full clinical trials might yield a similar result to Moderna’s Phase 2 trial, he said it isn’t clear if the manufacturer would even allow countries to stretch their supplies.

He also agreed keeping the current guidelines in place is the ideal approach for the time being, rather than risking lives by adopting a dosing strategy that needs more evidence.

“We don’t know where we are going,” Bach said. “You can put people in danger.”

Still, there’s some potential in Moderna’s early results, according to Chagla. 

Knowing the adequate dosing strategy will matter down the line while developing those boosters for variants, he said. And the early evidence points to the potential for increasing vaccine supply to much of the developing world, where shots remain in short supply.

“The answer will have implicating effects for years, not just the vaccine roll-out over the next few months,” Chagla said.

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