SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques

Yashavanth Shaan Lakshmanappa; Sonny R. Elizaldi; Jamin W. Roh; Brian A. Schmidt; Timothy D. Carroll; Kourtney D. Weaver; Justin C. Smith; Anil Verma; Jesse D. Deere; Joseph Dutra; Mars Stone; Sergej Franz; Rebecca Lee Sammak; Katherine J. Olstad; J. Rachel Reader; Zhong Min Ma; Nancy K. Nguyen; Jennifer Watanabe; Jodie Usachenko; Ramya Immareddy; Jo Ann L. Yee; Daniela Weiskopf; Alessandro Sette; Dennis Hartigan-O’Connor; Stephen J. McSorley; John H. Morrison; Nam K. Tran; Graham Simmons; Michael P. Busch; Pamela A. Kozlowski; Koen K.A. Van Rompay; Christopher J. Miller; Smita S. Iyer

doi:10.1038/s41467-020-20642-x

SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques

Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Brian A. Schmidt, Timothy D. Carroll, Kourtney D. Weaver, Justin C. Smith, Anil Verma, Jesse D. Deere, Joseph Dutra, Mars Stone, Sergej Franz, Rebecca Lee Sammak, Katherine J. Olstad, J. Rachel Reader, Zhong Min Ma, Nancy K. Nguyen, Jennifer Watanabe, Jodie Usachenko, Ramya ImmareddyJo Ann L. Yee, Daniela Weiskopf, Alessandro Sette, Dennis Hartigan-O’Connor, Stephen J. McSorley, John H. Morrison, Nam K. Tran, Graham Simmons, Michael P. Busch, Pamela A. Kozlowski, Koen K.A. Van Rompay, Christopher J. Miller, Smita S. Iyer

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Abstract

CD4 T follicular helper (T_fh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates T_fh 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 T_fh cells with a T_h1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a T_h1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC T_fh 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.

Original language	English
Article number	541
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-20642-x
State	Published - Dec 2021
Externally published	Yes

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Shaan Lakshmanappa, Y., Elizaldi, S. R., Roh, J. W., Schmidt, B. A., Carroll, T. D., Weaver, K. D., Smith, J. C., Verma, A., Deere, J. D., Dutra, J., Stone, M., Franz, S., Sammak, R. L., Olstad, K. J., Rachel Reader, J., Ma, Z. M., Nguyen, N. K., Watanabe, J., Usachenko, J., ... Iyer, S. S. (2021). SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques. Nature Communications, 12(1), Article 541. https://doi.org/10.1038/s41467-020-20642-x

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title = "SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques",

abstract = "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.",

author = "{Shaan Lakshmanappa}, Yashavanth and Elizaldi, {Sonny R.} and Roh, {Jamin W.} and Schmidt, {Brian A.} and Carroll, {Timothy D.} and Weaver, {Kourtney D.} and Smith, {Justin C.} and Anil Verma and Deere, {Jesse D.} and Joseph Dutra and Mars Stone and Sergej Franz and Sammak, {Rebecca Lee} and Olstad, {Katherine J.} and {Rachel Reader}, J. and Ma, {Zhong Min} and Nguyen, {Nancy K.} and Jennifer Watanabe and Jodie Usachenko and Ramya Immareddy and Yee, {Jo Ann L.} and Daniela Weiskopf and Alessandro Sette and Dennis Hartigan-O{\textquoteright}Connor and McSorley, {Stephen J.} and Morrison, {John H.} and Tran, {Nam K.} and Graham Simmons and Busch, {Michael P.} and Kozlowski, {Pamela A.} and {Van Rompay}, {Koen K.A.} and Miller, {Christopher J.} and Iyer, {Smita S.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41467-020-20642-x",

language = "English",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

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Shaan Lakshmanappa, Y, Elizaldi, SR, Roh, JW, Schmidt, BA, Carroll, TD, Weaver, KD, Smith, JC, Verma, A, Deere, JD, Dutra, J, Stone, M, Franz, S, Sammak, RL, Olstad, KJ, Rachel Reader, J, Ma, ZM, Nguyen, NK, Watanabe, J, Usachenko, J, Immareddy, R, Yee, JAL, Weiskopf, D, Sette, A, Hartigan-O’Connor, D, McSorley, SJ, Morrison, JH, Tran, NK, Simmons, G, Busch, MP, Kozlowski, PA, Van Rompay, KKA, Miller, CJ & Iyer, SS 2021, 'SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques', Nature Communications, vol. 12, no. 1, 541. https://doi.org/10.1038/s41467-020-20642-x

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.

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.

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U2 - 10.1038/s41467-020-20642-x

DO - 10.1038/s41467-020-20642-x

M3 - Article

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AN - SCOPUS:85099750901

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

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ER -

SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques

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