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Immunology: Circulating antibody and immune cell responses analyzed in patients recovering from COVID-19

Nature Medicine

July 13, 2020

Antibodies, memory B cells and circulating follicular helper T cells (cTFH cells) against the SARS-CoV-2 ‘spike’ were abundant in the plasma of 41 Australian adults who had recovered from COVID-19, but the ability of those antibodies and immune cells to neutralize and block the binding of the virus was inconsistent. The study, published in Nature Medicine, reports that although all of the studied patients who recovered from COVID-19 showed multiple hallmarks of immune recognition of the SARS-CoV-2 spike glycoprotein (which enables the virus to bind to and enter cells), the neutralizing ability of patients’ plasma varied widely, which suggests that vaccines may need to selectively target the most potent neutralizing epitopes.

A vaccine against SARS-CoV-2 is urgently needed, and approaches that elicit neutralizing antibodies that target the spike protein, blocking the binding of the virus to the human receptor protein ACE2, are appealing. However, although spike-based vaccine prototypes show promise in animal models, the spike-specific immune response in humans is not well understood.

Adam Wheatley, Stephen Kent and colleagues collected plasma and peripheral blood cells from 41 Australian adults, who had recovered from mild to moderate COVID-19, around 32 days after a positive PCR test. 24 were men and 17 were women, with a median age of 59 years. The authors found spike-specific antibodies, spike-specific memory B cells (a type of white blood cell that make antibodies), and spike-specific cTFH cells (a type of white blood cell that regulates B cell immunity) in all the study participants. However, the median capacity of the patients’ immune plasma to block the interaction between ACE2 and the viral binding site was modest (only about 14%). Statistical analysis revealed that the development of strong neutralizing activity in the plasma depended not only on the amount of spike-specific antibodies, but in addition, the relative abundance of distinct sub-populations of spike-specific cTFH cells expressing certain chemokine receptors.

These findings suggest that B cells and cTFH cells with specific surface and functional features might be useful targets for future vaccines, according to the authors. Further research with larger cohorts is needed to understand the interplay between cTFH cells and neutralizing antibodies elicited in response to different vaccines.

doi: 10.1038/s41591-020-0995-0

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