In the fight against COVID-19, antibodies are the best long-term weapon

A new study from the lab of Yale’s Akiko Iwasaki finds that antibodies, rather than T cells, are crucial in creating lasting protection from COVID-19.
Illustration of young woman wearing a facemask among COVID viruses in background.

(Illustration by Michael S. Helfenbein)

When it comes to long-lasting protection against COVID-19, antibodies — proteins created by B cells to neutralize invading pathogens — are our biggest allies, a new Yale study shows.

Since the emergence of the SARS-CoV-2 virus, the relative contributions of the different weapons within our immune system during and after infection — particularly of T cells, which destroy infected cells from the inside, and B cells, which produce antibodies that clean up free-floating virus outside of cells — have remained unclear.

To better understand them, scientists in the lab of Yale’s Akiko Iwasaki, the Waldemar Von Zedtwitz Professor of Immunobiology, conducted a series of experiments on mice to determine which immune system responses played the most important role in COVID-19 cases.

During acute infections, both immune responses played key roles in combatting infections, researchers found. Mice lacking T cells but with antibody protection and mice without antibodies but with healthy T cells both combatted infection equally well.

However, when mice lacking T cells — a kind of reserve cell that remains in the body after infection — were reinfected with SARS-CoV-2, the virus that causes COVID-19, antibodies alone provided more than adequate protection. The same was true when they were reinfected with the highly immune-evasive Beta variant. This antibody protection was also seen in mice that had received a vaccine.

While T cells play a role during acute infections, our antibodies are crucial for long-term protection against re-infection,” said Benjamin Goldman-Israelow, a postdoctoral researcher in Iwasaki’s lab and lead author of the study.

The paper was published Sept. 2 in the journal Science Immunology.

Goldman-Israelow stressed that previous research has shown that people who received mRNA-based vaccines produce more antibodies than those who were naturally infected. And naturally infected people who then received a vaccination produced even more antibodies, perhaps providing greater protection against re-infection.

While this study identified the importance of circulating antibodies in providing protection, the newly emerged Delta variant appears to overcome this systemic immunity to cause more breakthrough infections, he added.

Ultimately, generating robust mucosal immunity that involves both local antibodies and T cells will be key to preventing infection and disease,” Iwasaki said.

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Part of the In Focus Collection: Yale responds to COVID-19

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