As Vaccines Wane, Immune System Still Has Weapons Against Delta

Damian McNamara

August 16, 2021

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

More recent studies — but not all — show waning effectiveness of the mRNA vaccines to prevent SARS-CoV-2 infection, 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 preprint of a study by the Mayo Clinic, for example, reported high effectiveness at preventing SARS-CoV-2 infection during the Alpha variant period by the Moderna vaccine, at 86%, and Pfizer/BioNTech vaccine, at 76%. In contrast, with the more recent predominance of the Delta variant, the effectiveness of the Moderna vaccine dropped to 76% and that of the Pfizer vaccine dropped to 42%.

But protection against hospitalization with the Delta variant in circulation remained high for both vaccines, ranging from 75% to 81%.

How different parts of the immune system respond to SARS-CoV-2 infection might explain, at least in part, the disparity.

"It's very plausible," Alessandro Sette, DrBiolSci, told Medscape Medical News.

Neutralizing antibodies induced by COVID-19 vaccination circulate in the body, recognize and bind to the virus, and thereby prevent 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 a professor at the Center for Autoimmunity and Inflammation and Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology in California.

Enter the T Cells and B Cells

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

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

Whereas antibodies recognize the SARS-CoV-2 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 SARS-CoV-2 virus 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, three out of four 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 August 12. Topol is director of Scripps Translational Science Institute in La Jolla, California, and editor-in-chief of Medscape.

Topol also added a caveat that the Pfizer vaccine has been available longer than the Moderna vaccine. "There are now five mRNA vaccine effectiveness studies for preventing Delta infections, and more on the way. Except for @PHE_UK, all show a marked reduction, particularly for @Pfizer, but the @moderna_tx comparison is confounded by its later administration (less chance to see waning)," he wrote.

Similar to the Mayo Clinic report, these other researchers have verified the high protection the vaccines provide against 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.

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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