Since their initial clinical trials and adoption months ago, subtle differences between the Pfizer Inc.-BioNTech SE and Moderna Inc. vaccines have emerged, but the question remains -- how much impact do the distinctions have?
Ten months ago, the results of large clinical trials appeared almost too good to be true. Two messenger RNA vaccines reduced symptomatic covid-19 cases by more than 90% in almost every group that got them.
Now, one small U.S. study found waning levels of antibodies with Pfizer's vaccine, particularly in an older group of people. And a larger study from Belgium found that Moderna's shot may generate more antibodies than Pfizer's.
But what this all means in the real world is still unclear. While billions of doses of vaccine have been administered around the world, researchers are still working to understand the nuances of how long the vaccine protection lasts, and how it differs from one person to another.
Getting answers to those questions is a crucial step to determine who might need booster shots, especially for older people and those with weakened immune systems. The more-infectious delta variant, the rise of which has coincided with slight drop-offs in vaccine effectiveness, has raised the stakes and led governments to begin rolling out a third dose of the shots. The Food and Drug Administration will hear public arguments on Sept. 17 about whether to go ahead with booster shots of Pfizer's vaccine.
Much of the focus has been on levels of antibodies, which serve as one of the immune system's front-line defenses. One theory about Moderna's vaccine is that it creates more of those antibodies because it uses a larger dose and the two doses are administered over a one-week longer period than Pfizer's.
But antibodies are just one component of immunity, and it isn't clear if they are the most important one, especially over the long-term.
"Do we know an antibody level that protects against covid? The simple answer is we still do not know that," said Paul Burton, Moderna's chief medical officer, on Friday. Still, Moderna's trial data show that a third shot six months after the second raises antibody levels "well into that comfort zone" back above levels seen in the initial phase 3 trial.
Along with shorter-lasting antibodies, covid-19 vaccines also trigger what's essentially a long-term memory in the immune system. That memory appears to increase and become better at making variant-fighting antibodies over time. That longer-term protection, which includes what are known as T cells and memory B cells, is harder to measure in the lab than antibodies.
But it's thought to play an important role in preventing severe illness and hospitalizations.
But less than a year into the vaccine campaign, much of the research has focused on vaccine-derived antibodies, which help lock onto an invading pathogen and tag it for attack by the rest of the immune system.
A small U.S. study examined a group of nursing-home patients and staff members who got two doses of the Pfizer vaccine. It found antibody levels in both groups waned over time. But the 120 residents in the study, who had a median age of 76, started out with a much lower level of antibodies than the younger staff did.
Over a number of months, "they end up in an even worse spot," said David Canaday, an infectious disease physician and professor of medicine at Case Western Reserve University in Cleveland, Ohio, who led the study, which was released as a preprint before publication in late August.
Two weeks after a second inoculation, neutralizing antibodies had fallen below the level of detection in 16% of nursing home residents who hadn't had covid-19 before their immunizations. Six months post-vaccination, 70% had extremely low levels.
By contrast, only 16% of the 64 younger caregivers had such meager antibodies six months out, the research found.
"Definitely the protection will drop a fair amount with these levels of antibody loss," Canaday said. But it's unlikely such a loss will mean zero protection.
A second study compared antibody levels in 167 University of Virginia health system staff immunized with either the Moderna or Pfizer vaccine. Antibodies levels after the second vaccine were about 50% higher in people who got the Moderna shot, the researchers said Thursday in a letter in Jama Network Open.
But when the researchers dug further, they found that the difference was mostly explained by an inferior response to the Pfizer vaccine in people 50 and older, says Jeffrey Wilson, an immunologist at the University of Virginia and co-author on the study.
With the Moderna vaccine, the antibody response after two shots didn't differ dramatically by age group.
"There are probably subtle differences between Pfizer and Moderna," said Wilson. "Whether that has a clinically meaningful impact on protection against the virus remains to be seen."
Protection against severe disease and hospitalization -- the most important public-health benefit of vaccination -- has generally remained strong.
"We're not seeing the hospitals filling up with vaccinated people," says Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan in Saskatoon. "What we're seeing is mostly unvaccinated people still making up the bulk of the new cases."