By Kate Kelland and Julie Steenhuysen
LONDON/CHICAGO, Jan 5 (Reuters) - Britain and other nations
are considering ways to stretch scarce supplies of COVID-19
vaccines, including by delaying second doses, reducing dose
sizes and switching vaccine types between the first and second
shots.
The proposals have generated fierce debate among scientists.
Here is the rationale behind, and criticism of, these
alternative strategies:
WHY DELAY THE SECOND DOSE?
In clinical trials, companies tested specific doses of their
vaccines at precise time intervals to generate evidence showing
how well they work. All COVID-19 vaccines approved, so far, are
designed to teach the immune system to recognise and defend
against the virus with a first dose, and then provide a second
booster dose to reinforce that lesson.
Faced with a fast-spreading pandemic and new, more
transmissible coronavirus variants, some countries are hoping to
widen immunisation by giving some protection to as many people
as possible with a first dose, and delaying second doses.
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", said Michael Head, a global
health expert at Britain's University of Southampton.
For a FACTBOX on countries' dosing intervals, click here:
WHAT ABOUT SWITCHING BETWEEN COVID VACCINES?
Mixing or switching between COVID-19 vaccines is largely
driven by the same aim - vaccinating as many people as possible
as the pandemic still rages.
Giving a priming dose of one vaccine and a booster dose of
another offers flexibility to offer whichever shots are
available, rather than holding shots back so individuals always
get both doses of the same vaccine.
HAVE THESE STRATEGIES BEEN TESTED IN RIGOROUS TRIALS?
No.
None of the late-stage COVID-19 vaccine trials compared
these dose-sparing strategies or the effects of mixing vaccine
types, said Stephen Evans, a professor of pharmacoepidemiology
at the London School of Hygiene & Tropical Medicine (LSHTM).
Officials have cited limited evidence from trials that the
Pfizer/BioNTech , the Oxford
University/AstraZeneca and the Moderna vaccines
all confer some protection against COVID-19 after the first
dose.
Britain's MHRA health regulator said on Dec. 30 it had found
an 80% success rate for the Oxford/AstraZeneca vaccine when two
full doses are administered, three months apart, higher than the
average that the developers themselves had found.
The UK government's vaccine advisory committee said on Dec.
31 that the Pfizer/BioNTech vaccine conferred 89% protection
from two weeks after the first dose, and that for the
Oxford/AstraZeneca vaccine "the evidence shows that the initial
dose ... offers as much as 70% protection against the effects of
the virus". It did not give detailed data.
Moderna reported its vaccine was 80% protective after one
dose, with efficacy peaking two weeks after the first shot.
But 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.
BioNTech and Pfizer warned on Monday they had no evidence
their vaccine would continue to be protective if the second dose
was given more than 21 days after the first.
Evans said that ideally "it is safest and most cautious" to
use vaccines in conditions exactly matching those of their
trials, but added: "In the real world, this is never so."
Anthony Fauci, director of the U.S. National Institute of
Allergy and Infectious Diseases, told CNN on Friday the United
States was unlikely to delay giving second doses.
"We're going to keep doing what we're doing," he said.
Likewise, scientists have raised concerns over the idea of
mixing two different types of vaccines. Some experts speculate
that, because all of the vaccines target the same outer "spike"
protein of the virus, they could work together to train the body
to fight off the virus.
But there is no evidence this approach will work.
"There is literally zero data. It has not been tested, or if
it has been tested, the data have not been made available," said
John Moore, a professor of microbiology and immunology at Weill
Cornell Medical College in New York.
WHAT ABOUT REDUCING THE AMOUNT OF VACCINE IN EACH DOSE?
In the United States, some health officials are considering
offering half doses of Moderna's vaccine to individuals aged 18
to 55. There is some clinical trial data backing this strategy.
Moncef Slaoui, chief adviser to the U.S. vaccine programme
Operation Warp Speed, told CBS on Sunday that evidence from a
Moderna trial showed the half dose induced an "identical immune
response" to the higher 100 microgram dose in adults aged 55 and
under. He said the U.S. government was discussing the issue with
Moderna and regulators.
Slaoui said he believed injecting half of the volume of
vaccine was "a more responsible approach that would be based on
facts and data".
Several U.S. scientists agreed, but noted the data was not
publicly available. "It's very fuzzy. I want to see that data,"
said Eric Topol, a genomics expert and director of the Scripps
Research Translational Institute in La Jolla, California.
SO ARE THESE STRATEGIES SAFE? AND WILL THEY WORK?
It's not clear.
While there is no scientific evidence on the impact of
delaying COVID-19 vaccine doses, some experts believe it could
be safe to wait and the potential payoff in protecting a larger
swath of the population may be worth it.
Others aren't so sure.
"There's just no data," said Ian Jones, a professor of
virology at Britain's Reading University.
The British Society of Immunology said in a statement on
Monday that delaying a second dose by eight weeks "would be
unlikely to have a negative effect on the overall immune
response". It added that it would not expect any extra safety
risks from the delay beyond the potential increased risk of
disease during the interim between doses.
Some scientists also said that while there was no evidence
to support the strategy of mixing vaccine doses from different
manufacturers - a method known as heterologous prime-boost -
evidence from other vaccines provided some reassurance.
"Based on previous studies which combine different vaccine
types, a combination of the AstraZeneca and Pfizer vaccines is
likely to be safe," said Helen Fletcher, a professor of
immunology at LSHTM.
Topol called the mix-and-match strategy "a big mistake" with
"unpredictable" results - including the potential for adverse
reactions or a significant drop-off in efficacy. "It makes no
sense whatsoever," he said.
Some worry about safety issues, particularly with delaying
the second dose for several weeks. The gap could allow time for
the virus to evolve and develop resistance to the vaccine.
Weak antibody protection could also increase the risk of
having an abnormal immune response - such as antibody-dependent
enhancement - when people encounter the real virus, Topol said.
HOW PRACTICAL IS IT TO PROLONG DOSING TIME SCHEDULES?
Extending the interval poses adherence risks, raising the
chance people may forget or fail to return for a second dose.
It also increases the length of time during which they are
less than optimally protected, and it could make it harder for
health authorities to keep track of who has had which vaccine,
when, and how often.
Given these risks, immunology and public health experts say
clear communication is imperative to ensure people understand
that although dosing schedules may be subject to change, two
COVID-19 vaccine doses are needed to give the best protection.
(Reporting by Kate Kelland and Julie Steenhuysen. Additional
reporting by Michael Erman in New Jersey. Editing by Josephine
Mason and Mark Potter)
Astrazeneca (AZN)
