TY - JOUR
T1 - SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques
AU - Shaan Lakshmanappa, Yashavanth
AU - Elizaldi, Sonny R.
AU - Roh, Jamin W.
AU - Schmidt, Brian A.
AU - Carroll, Timothy D.
AU - Weaver, Kourtney D.
AU - Smith, Justin C.
AU - Verma, Anil
AU - Deere, Jesse D.
AU - Dutra, Joseph
AU - Stone, Mars
AU - Franz, Sergej
AU - Sammak, Rebecca Lee
AU - Olstad, Katherine J.
AU - Rachel Reader, J.
AU - Ma, Zhong Min
AU - Nguyen, Nancy K.
AU - Watanabe, Jennifer
AU - Usachenko, Jodie
AU - Immareddy, Ramya
AU - Yee, Jo Ann L.
AU - Weiskopf, Daniela
AU - Sette, Alessandro
AU - Hartigan-O’Connor, Dennis
AU - McSorley, Stephen J.
AU - Morrison, John H.
AU - Tran, Nam K.
AU - Simmons, Graham
AU - Busch, Michael P.
AU - Kozlowski, Pamela A.
AU - Van Rompay, Koen K.A.
AU - Miller, Christopher J.
AU - Iyer, Smita S.
N1 - Funding Information:
We are grateful to Lourdes Adamson and Nicole Drazenovich for BSL-3 training and facilitating access to CIID BSL-3. The authors are grateful to Greg Hodges for facilitating the animal experiments in CNPRC ABSL3. We are extremely grateful to the primate center staff Wilhelm Von Morgenland, Miles Christensen, David Bennet, Vanessa Bakula, James Schulte, Jose Montoya, Joshua Holbrook, John McAnelly, Christopher Nelson, and David Bennett for animal sampling in ABSL3 at the CNPRC. Mark Allen provided necropsy technical expertise in the BSL-3 necropsy suite. The authors are grateful to Amanda Carpenter, Peter Nham, and Bryson Halley at the Primate Assay Laboratory Core. We thank Larry Dumont at VIR for the CP and Linda Fritts for assistance with PCR assays. We are grateful to David Asmuth for facilitating IRB approval to procure clinical samples. We thank Jeffrey Roberts, Lisa Miller, Marcelo Kuroda for their support in facilitating these experiments and acknowledge assay resources provided by the Primate Assay Laboratory Core and CNPRC base grant. The 10F12 anti-monkey IgA monoclonal antibody was obtained from the NIH Nonhuman Primate Reagent Resource supported by AI126683 and OD010976. This work was supported by internal seed grants to CNRPC and CIID, R21 AI143454-02S1 (S.S.I.), FAST GRANT—George Mason University (S.S.I.), NIH Contract # 75N9301900065 (A.S. and D.W), and the CNPRC base grant P51OD011107.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.
AB - CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.
UR - http://www.scopus.com/inward/record.url?scp=85099750901&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-20642-x
DO - 10.1038/s41467-020-20642-x
M3 - Article
C2 - 33483492
AN - SCOPUS:85099750901
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 541
ER -