Aug. 16, 2021 -- More recent studies — but not all — show Moderna’s and Pfizer’s COVID-19 vaccines become less effective at blocking infection with the coronavirus over time, especially with high levels of the Delta variant going around. At the same time, the vaccines continue to offer robust protection against severe COVID-19 outcomes.

A Mayo Clinic study, for example, found the Moderna vaccine had an 86% effective rate at preventing infection with the Alpha variant, compared to 76% for Pfizer’s vaccine.

But, against the Delta variant, Moderna’s effectiveness fell to 76% and Pfizer’s dropped all the way to 42%.

The Mayo study has not been peer-reviewed yet.

Still, both vaccines continue offer strong protection against hospitalization, with an effectiveness ranging from 75% to 81%.

How different parts of the immune system respond to coronavirus infection might explain, at least in part, the disparity.

"It's very plausible," Alessandro Sette, doctor of biological science, says.

Neutralizing antibodies from COVID-19 vaccination circulate in the body, recognize and bind to the virus, and stop it from entering cells and replicating. "That is arguably why we have cell immunity," Sette said.

However, once the virus enters a cell, it is no longer accessible to the antibodies, explained Sette, who is professor at the Center for Autoimmunity and Inflammation and Center for Infectious Disease and Vaccine Research at the La Jolla Institute for Immunology in California.

Enter the T Cells and B Cells

"The immune system really works in concert against invaders," Sette said, and is like bringing in the army, navy, and air force at the same time to fight a war, he added.

There are two types of T cells. Helper T cells recognize infected cells and stimulate B cells to make antibodies to fight the virus. Killer T cells, which as the name suggests, can recognize and eliminate infected cells.

"T cells in particular have the capacity, not so much to prevent the infection, but to modulate or terminate the infection," Sette explained.

While antibodies recognize the coronavirus spike protein, T cells spot fragments of the virus left on the cell surface after a virus replicates inside.

Although antibodies can lose some ability to neutralize a variant, "what we and other labs have shown is the T cell response remains unaffected," Sette said. Therefore, even if the virus gets past the vaccine antibody line of defense and enters cells, T cells can still attack.

"This is exactly what we are seeing," Sette added. "Obviously, this is good news."

Furthermore, the memory B cells charged with making antibodies have a "fascinating capacity" to adapt and change over time to help neutralize an infection, he said.

A Race Against Time

Sette's colleague at the La Jolla Institute for Immunology, Shane Crotty, PhD, noted on Twitter that B cells and T cells are among the fastest replicating cells in the body, and multiply for several days to produce enough to neutralize an infection.

However, the coronavirus also replicates quickly.

"If the virus is 2-3 days faster (4 days), that is a much harder ask of the T cells and B cells to stop the virus fast enough to prevent symptoms (and transmission). That means it is a variant with more burden on the neutralizing antibodies to stop up front," he noted on Twitter.

A General Consensus

In addition to the Mayo Clinic study, 3 out of 4 other recent studies evaluating mRNA COVID-19 vaccine protection against the Delta variant revealed a drop-off in effectiveness.

The relatively low 40% effectiveness reported by Israeli officials, for example, "was met with disbelief," Eric Topol, MD, pointed out on Twitter Aug. 12. Topol is director of Scripps Translational Science Institute in La Jolla, CA, and editor-in-chief of Medscape.

Similar to the Mayo Clinic report, these other researchers have verified the high protection these vaccines provide versus severe outcomes, hospitalization, and death.

These new data are not the same as those released by Pfizer showing overall vaccine effectiveness drops from 96% to 84% after 6 months.

"This reduction of protection is quite different from the 6-month follow up of the Pfizer and Moderna pivotal trials which showed modest decline, but were against the original strain, not Delta," Topol tweeted.