Open AccessSARS-CoV-2-specific circulating T follicular helper cells correlate with neutralizing antibodies and increase during early convalescence
Author(s) -
Sushma Boppana,
Kai Qin,
Jacob K. Files,
Ronnie M. Russell,
Regina Stoltz,
Frédéric Bibollet-Ruche,
Anju Bansal,
Nathan Erdmann,
Beatrice H. Hahn,
Paul A. Goepfert
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1009761
Subject(s) - convalescence , antibody , immunology , neutralizing antibody , virology , neutralization , antibody response , biology , immune system , antigen , convalescent plasma , t cell , medicine , covid-19 , disease , infectious disease (medical specialty)
T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 26 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mounted at least one CD4 T-cell response, and 48% of individuals mounted detectable SARS-CoV-2-specific circulating T follicular helper cells (cTfh, defined as CXCR5 + PD1 + CD4 T cells). SARS-CoV-2-specific cTfh responses across all three protein specificities correlated with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, cTfh responses, particularly to the M protein, increased in convalescence, and robust cTfh responses with magnitudes greater than 5% were detected at the second convalescent visit, a median of 38 days post-symptom onset. CD4 T-cell responses declined but persisted at low magnitudes three months and six months after symptom onset. These data deepen our understanding of antigen-specific cTfh responses in SARS-CoV-2 infection, suggesting that in addition to S protein, M and N protein-specific cTfh may also assist in the development of neutralizing antibodies and that cTfh response formation may be delayed in SARS-CoV-2 infection.