To find out how vaccines are holding up in the running battle against COVID-19, Anne-Claude Gingras is being guided by the lights.
In her lab at Mount Sinai Hospital in Toronto, Dr. Gingras is culturing cells that have been engineered to glow when they are infected with the coronavirus. The approach is a standard laboratory technique that can be used to see if antibodies from vaccinated individuals can block infection. Dr. Gingras is using it to study how that blocking ability is compromised by emerging COVID-19 variants.
“We can get a really good measurement of neutralization by looking at how much light production in the cells is decreased,” said Dr. Gingras, who is a senior investigator at the hospital’s Lunenfeld-Tanenbaum Research Institute.
With this setup, Dr. Gingras and her colleagues can recreate a breakthrough infection – a situation where the coronavirus manages to defeat the antibodies that vaccination has raised against it. That scenario is top of mind for Canadian public-health officials as they grapple with the fourth wave of the pandemic, propelled by the Delta variant, which is the most contagious version of COVID-19 so far.
As of Friday, new cases are rising steadily across Canada, in the range of 3,000 per day. That is comparable to the national picture in late May. In contrast, the number of cases in hospital are just a quarter of what they were then, a sign that vaccines are preventing many cases from becoming serious. But the upward trend is still a worry, in part because fully one-third of the country remains unvaccinated, including all children under 12. That has left plenty of room for the pandemic to keep rolling with a new, more transmissible variant that seems almost impossible to dodge without the aid of a vaccine.
“There’s no way to crush the fourth wave without going back into a lockdown – and we do not want that – so we have to mitigate it,” said Peter Juni, the scientific director of Ontario’s COVID-19 Science Advisory Table and a professor of medicine and epidemiology at the University of Toronto.
Key to the mitigation effort is understanding that while vaccines are essential for protecting against severe illness, they are unable to completely shut down infection and transmission – a reality that viral evolution, via coronavirus variants, is now taking advantage of. This is likely to become more of an issue as immunity wanes among those who were first to receive their shots.
There are signs that some parts of the world are already encountering problems with weakening immunity from vaccination. For example, Israel, which began its vaccination campaign well ahead of other countries, is now experiencing an increasing rate of breakthrough infections. Last week, it became the first country to offer third doses to those who are 50 or older. On Wednesday, the United States said it would also begin rolling out third doses starting next month. The move toward additional protection has been hastened by the near absence of public-health measures in many states.
Canada has not yet reached the third dose threshold – with the important exception of people who are immune compromised, such as transplant patients – but it’s likely heading in that direction. According to the Public Health Agency of Canada, by the beginning of this month about 0.03 per cent of fully vaccinated Canadians had become infected with COVID-19. While the number of breakthrough infections is small, the prevalence of the Delta variant ensures that it will grow.
New data shared by Ontario’s science table puts the current situation in focus. The ratio of cases between unvaccinated and vaccinated individuals now stands at roughly 10 to 1 in Ontario. The ratios are closer 30 to 1 and 75 to 1 for COVID-19 cases currently in hospital and in intensive care units, respectively, when figures are adjusted to take into account both the lower disease risk and lower vaccination rate among younger people. Vaccinated individuals are also about 10 times less likely to get long COVID-19, when symptoms persist for months or longer, Dr. Juni said, although this estimate is based on limited studies.
Put another way, in a room full of 100 Canadians that are representative of the entire population, 35 individuals will currently be unvaccinated. Over time, nearly all of those unvaccinated people, about 33 of them, can expect to become infected as the virus circulates in the room. About six cases would be expected to arise among the fully vaccinated group. Bottom line: we can assume that only about 60 people in the room of 100 are “safe” from infection.
What this means is that while vaccines drastically improve the odds for those who take them, vaccinated people can still be infected and they can play a significant role in transmitting COVID-19 to the unvaccinated.
As a result, distancing, face masks and limiting discretionary gatherings will remain important tools for controlling the fourth wave. Such efforts will buy time until regulators give the green light for children to be vaccinated, and until more of those who are hesitant decide to take the shot. But, as time passes, more breakthrough infections can be expected.
This breakthrough cycle is what the Mount Sinai team is investigating with the help of its glowing cell cultures. Dr. Gingras and her colleagues take a type of virus called a lentivirus, dress it up with proteins that are identical to those that are associated with the COVID-19 variants, and then expose it to antibodies from vaccinated people.
On Tuesday, the team released the results of an immunity study of vaccinated Ontario long-term care residents and staff. Although it has not yet been peer reviewed, it offers a window onto fluctuating immunity levels among Canadians as waves of new variants sweep through the population. It’s a reminder that the protection vaccines offer is not so much a brick wall as it is a hedgerow – a living barrier that can be breached and that becomes patchy over time if it is not maintained.
What the data show is that the initial variants that arrived in Canada several months ago can resist vaccines to different degrees. Alpha, the variant that drove the third wave of the pandemic, is blocked by vaccine antibodies to nearly the same degree as the original Wuhan strain of COVID-19. Much more vaccine resistant is the Beta variant, which arrived at about the same time as Alpha. Fortunately, it was outcompeted by Alpha because it is less contagious.
Somewhere in the middle lies the Gamma variant, first identified in Brazil. It produced significant outbreaks in Canada earlier this year, and in April it was identified as the culprit behind 19 breakthrough cases among vaccinated residents in an Ontario long-term care facility, two of whom died.
In a yet-to-be-released update to the long-term care study, the team determined that the Delta variant is about as good as Gamma at evading antibodies. However, it is also far more transmissible than Alpha, which means that many more Canadians are now being exposed to it, including those whose immune responses may not be adequate to prevent infection despite being vaccinated.
Not surprisingly, the Mount Sinai study also found that the antibody response to the variants was better among long-term care staff, regardless of which vaccine they had received, than it was among residents. This was simply a function of the staff being younger. Immunity is harder to maintain as we age, and so it’s among older individuals that we should expect to see signs of breakthrough infections showing up first.
Among the residents in the study, those who received the Moderna vaccine did better against the variants than those who received Pfizer. The Moderna shot has a higher dose of the vaccines’ active ingredient – the messenger RNA that is used by cells as a blueprint for making coronavirus proteins to activate the immune system – but Dr. Gingras said it’s not yet clear if that’s the reason why Moderna’s product appeared to produce a more robust immune response.
More data will be needed to show how immunity decreases with time – a trajectory that will help determine when booster shots are needed.
For now, booster vaccines will still use the genetic recipe derived from the strain of the virus that was prevalent in the world over a year ago. The aim is to give the body’s immune system a bigger club – rather than a better one – to fight the variants. But vaccine makers are also testing new recipes tailored to various mutations that have appeared among some of the variants.
“We are nowhere close to saying that any of these variants are [entirely] immune resistant, and that is a good place to be,” said Marc-André Langlois, a molecular virologist at the University of Ottawa.
The longer-term worry is vaccine escape, in which a new variant emerges with a combination of mutations that render vaccines completely ineffective. Against that troubling scenario, the Delta variant may become our unlikely ally, simply because its high rate of transmission makes it harder for other variants to gain a foothold even if they are more resistant to vaccines.
“Delta is very difficult to out-compete,” Dr. Juni said. “I still keep my fingers crossed that evolution has maxed out and there’s nothing worse to come... But who knows.”
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