B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

Samantha M. Townsley; Gina C. Donofrio; Ningbo Jian; David J. Leggat; Vincent Dussupt; Letzibeth Mendez-Rivera; Leigh Anne Eller; Lauryn Cofer; Misook Choe; Philip K. Ehrenberg; Aviva Geretz; Syna Gift; Rebecca Grande; Anna Lee; Caroline Peterson; Mary Bryson Piechowiak; Bonnie M. Slike; Ursula Tran; M. Gordon Joyce; Ivelin S. Georgiev; Morgane Rolland; Rasmi Thomas; Sodsai Tovanabutra; Nicole A. Doria-Rose; Victoria R. Polonis; John R. Mascola; Adrian B. McDermott; Nelson L. Michael; Merlin L. Robb; Shelly J. Krebs

doi:10.1016/j.chom.2021.01.016

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

Samantha M. Townsley, Gina C. Donofrio, Ningbo Jian, David J. Leggat, Vincent Dussupt, Letzibeth Mendez-Rivera, Leigh Anne Eller, Lauryn Cofer, Misook Choe, Philip K. Ehrenberg, Aviva Geretz, Syna Gift, Rebecca Grande, Anna Lee, Caroline Peterson, Mary Bryson Piechowiak, Bonnie M. Slike, Ursula Tran, M. Gordon Joyce, Ivelin S. GeorgievMorgane Rolland, Rasmi Thomas, Sodsai Tovanabutra, Nicole A. Doria-Rose, Victoria R. Polonis, John R. Mascola, Adrian B. McDermott, Nelson L. Michael, Merlin L. Robb, Shelly J. Krebs^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.

Original language	English
Pages (from-to)	564-578.e9
Journal	Cell Host and Microbe
Volume	29
Issue number	4
DOIs	https://doi.org/10.1016/j.chom.2021.01.016
State	Published - 14 Apr 2021
Externally published	Yes

Keywords

B cells
HIV
acute infection
broadly neutralizing antibodies
founder envelope

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10.1016/j.chom.2021.01.016

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Townsley, S. M., Donofrio, G. C., Jian, N., Leggat, D. J., Dussupt, V., Mendez-Rivera, L., Eller, L. A., Cofer, L., Choe, M., Ehrenberg, P. K., Geretz, A., Gift, S., Grande, R., Lee, A., Peterson, C., Piechowiak, M. B., Slike, B. M., Tran, U., Joyce, M. G., ... Krebs, S. J. (2021). B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies. Cell Host and Microbe, 29(4), 564-578.e9. https://doi.org/10.1016/j.chom.2021.01.016

@article{12ca580b7f6440c7a5683e73be475590,

title = "B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies",

abstract = "Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.",

keywords = "B cells, HIV, acute infection, broadly neutralizing antibodies, founder envelope",

author = "Townsley, {Samantha M.} and Donofrio, {Gina C.} and Ningbo Jian and Leggat, {David J.} and Vincent Dussupt and Letzibeth Mendez-Rivera and Eller, {Leigh Anne} and Lauryn Cofer and Misook Choe and Ehrenberg, {Philip K.} and Aviva Geretz and Syna Gift and Rebecca Grande and Anna Lee and Caroline Peterson and Piechowiak, {Mary Bryson} and Slike, {Bonnie M.} and Ursula Tran and Joyce, {M. Gordon} and Georgiev, {Ivelin S.} and Morgane Rolland and Rasmi Thomas and Sodsai Tovanabutra and Doria-Rose, {Nicole A.} and Polonis, {Victoria R.} and Mascola, {John R.} and McDermott, {Adrian B.} and Michael, {Nelson L.} and Robb, {Merlin L.} and Krebs, {Shelly J.}",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = apr,

day = "14",

doi = "10.1016/j.chom.2021.01.016",

language = "English",

volume = "29",

pages = "564--578.e9",

journal = "Cell Host and Microbe",

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Townsley, SM, Donofrio, GC, Jian, N, Leggat, DJ, Dussupt, V, Mendez-Rivera, L, Eller, LA, Cofer, L, Choe, M, Ehrenberg, PK, Geretz, A, Gift, S, Grande, R, Lee, A, Peterson, C, Piechowiak, MB, Slike, BM, Tran, U, Joyce, MG, Georgiev, IS, Rolland, M, Thomas, R, Tovanabutra, S, Doria-Rose, NA, Polonis, VR, Mascola, JR, McDermott, AB, Michael, NL, Robb, ML & Krebs, SJ 2021, 'B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies', Cell Host and Microbe, vol. 29, no. 4, pp. 564-578.e9. https://doi.org/10.1016/j.chom.2021.01.016

TY - JOUR

T1 - B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

AU - Townsley, Samantha M.

AU - Donofrio, Gina C.

AU - Jian, Ningbo

AU - Leggat, David J.

AU - Dussupt, Vincent

AU - Mendez-Rivera, Letzibeth

AU - Eller, Leigh Anne

AU - Cofer, Lauryn

AU - Choe, Misook

AU - Ehrenberg, Philip K.

AU - Geretz, Aviva

AU - Gift, Syna

AU - Grande, Rebecca

AU - Lee, Anna

AU - Peterson, Caroline

AU - Piechowiak, Mary Bryson

AU - Slike, Bonnie M.

AU - Tran, Ursula

AU - Joyce, M. Gordon

AU - Georgiev, Ivelin S.

AU - Rolland, Morgane

AU - Thomas, Rasmi

AU - Tovanabutra, Sodsai

AU - Doria-Rose, Nicole A.

AU - Polonis, Victoria R.

AU - Mascola, John R.

AU - McDermott, Adrian B.

AU - Michael, Nelson L.

AU - Robb, Merlin L.

AU - Krebs, Shelly J.

PY - 2021/4/14

Y1 - 2021/4/14

N2 - Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.

AB - Determining which immunological mechanisms contribute to the development of broad neutralizing antibodies (bNAbs) during HIV-1 infection is a major goal to inform vaccine design. Using samples from a longitudinal HIV-1 acute infection cohort, we found key B cell determinants within the first 14–43 days of viremia that predict the development of bNAbs years later. Individuals who develop neutralization breadth had significantly higher B cell engagement with the autologous founder HIV envelope (Env) within 1 month of initial viremia. A higher frequency of founder-Env-specific naive B cells was associated with increased B cell activation and differentiation and predictive of bNAb development. These data demonstrate that the initial B cell interaction with the founder HIV Env is important for the development of broadly neutralizing antibodies and provide evidence that events within HIV acute infection lead to downstream functional outcomes.

KW - B cells

KW - HIV

KW - acute infection

KW - broadly neutralizing antibodies

KW - founder envelope

UR - http://www.scopus.com/inward/record.url?scp=85104079663&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2021.01.016

DO - 10.1016/j.chom.2021.01.016

M3 - Article

C2 - 33662277

AN - SCOPUS:85104079663

SN - 1931-3128

VL - 29

SP - 564-578.e9

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 4

ER -

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

Abstract

Keywords

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