The Columbus Dispatch

Study: 1 COVID-19 vaccine may make more antibodies

- Jason Gale and Robert Langreth

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, subtle differences between the Pfizer Inc.-biontech SE and Moderna Inc. vaccines are emerging across patient groups over time. One small U.S. study found waning levels of antibodies with Pfizer’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 Pfizer’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 their protection lasts, and how it differs from one person to another.

Getting answers to those questions is a crucial step to determine who might need a booster shot, especially for older people and those with weakened immune systems.

The more infectious delta variant, the rise of which has coincided with slight drop-offs in vaccine effectiveness, 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 Pfizer’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 interval than Pfizer’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 officer, in a Friday call with reporters. 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-fighting 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 who got two doses of the Pfizer 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.

“Definitely 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 Pfizer 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 difference was mostly explained by an inferior response to the Pfizer vaccine in people 50 and older, says Jeffrey 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 differ dramatical­ly by age group.

“There are probably subtle differences between Pfizer and Moderna,” said Wilson. “Whether that has a clinically meaningful impact on protection against the virus remains to be seen.”

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