Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

Isabella Huettner; Stefanie A. Krumm; Sonia Serna; Katarzyna Brzezicka; Serena Monaco; Samuel Walpole; Angela Van Diepen; Fiona Allan; Thomas Hicks; Simon Kimuda; Aidan M. Emery; The IAVI Protocol C Investigators & The IAVI African HIV Research Network; Susan Allen; William Kilembe; Shabir Lakhi; Mubiana Inambao; Etienne Karita; Anatoli Kamali; Eduard J. Sanders; Omu Anzala; Vinodh Edward; Linda-Gail Bekker; Jianming Tang; Jill Gilmour; Eric Hunter; Matt Price; Elise Landais; Cornelis H. Hokke; Jesus Angulo; Niels Reichardt; Katie J. Doores

doi:10.1016/j.celrep.2022.110611

Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

Isabella Huettner, Stefanie A. Krumm, Sonia Serna, Katarzyna Brzezicka, Serena Monaco, Samuel Walpole, Angela Van Diepen, Fiona Allan, Thomas Hicks, Simon Kimuda, Aidan M. Emery, The IAVI Protocol C Investigators & The IAVI African HIV Research Network, Susan Allen, William Kilembe, Shabir Lakhi, Mubiana Inambao, Etienne Karita, Anatoli Kamali, Eduard J. Sanders, Omu AnzalaVinodh Edward, Linda-Gail Bekker, Jianming Tang, Jill Gilmour, Eric Hunter, Matt Price, Elise Landais, Cornelis H. Hokke, Jesus Angulo, Niels Reichardt, Katie J. Doores

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Abstract

The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.

Original language	English
Article number	110611
Journal	Cell Reports
Volume	38
Issue number	13
DOIs	https://doi.org/10.1016/j.celrep.2022.110611
Publication status	Published - 29 Mar 2022

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Cite this

Huettner, I., Krumm, S. A., Serna, S., Brzezicka, K., Monaco, S., Walpole, S., Van Diepen, A., Allan, F., Hicks, T., Kimuda, S., Emery, A. M., The IAVI Protocol C Investigators & The IAVI African HIV Research Network, Allen, S., Kilembe, W., Lakhi, S., Inambao, M., Karita, E., Kamali, A., Sanders, E. J., ... Doores, K. J. (2022). Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans. Cell Reports, 38(13), [110611]. https://doi.org/10.1016/j.celrep.2022.110611

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title = "Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans",

abstract = "The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.",

author = "Isabella Huettner and Krumm, {Stefanie A.} and Sonia Serna and Katarzyna Brzezicka and Serena Monaco and Samuel Walpole and {Van Diepen}, Angela and Fiona Allan and Thomas Hicks and Simon Kimuda and Emery, {Aidan M.} and {The IAVI Protocol C Investigators & The IAVI African HIV Research Network} and Susan Allen and William Kilembe and Shabir Lakhi and Mubiana Inambao and Etienne Karita and Anatoli Kamali and Sanders, {Eduard J.} and Omu Anzala and Vinodh Edward and Linda-Gail Bekker and Jianming Tang and Jill Gilmour and Eric Hunter and Matt Price and Elise Landais and Hokke, {Cornelis H.} and Jesus Angulo and Niels Reichardt and Doores, {Katie J.}",

year = "2022",

month = mar,

day = "29",

doi = "10.1016/j.celrep.2022.110611",

language = "English",

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Huettner, I, Krumm, SA, Serna, S, Brzezicka, K, Monaco, S, Walpole, S, Van Diepen, A, Allan, F, Hicks, T, Kimuda, S, Emery, AM, The IAVI Protocol C Investigators & The IAVI African HIV Research Network, Allen, S, Kilembe, W, Lakhi, S, Inambao, M, Karita, E, Kamali, A, Sanders, EJ, Anzala, O, Edward, V, Bekker, L-G, Tang, J, Gilmour, J, Hunter, E, Price, M, Landais, E, Hokke, CH, Angulo, J, Reichardt, N & Doores, KJ 2022, 'Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans', Cell Reports, vol. 38, no. 13, 110611. https://doi.org/10.1016/j.celrep.2022.110611

TY - JOUR

T1 - Cross-reactivity of glycan-reactive HIV-1 broadly neutralizing antibodies with parasite glycans

AU - Huettner, Isabella

AU - Krumm, Stefanie A.

AU - Serna, Sonia

AU - Brzezicka, Katarzyna

AU - Monaco, Serena

AU - Walpole, Samuel

AU - Van Diepen, Angela

AU - Allan, Fiona

AU - Hicks, Thomas

AU - Kimuda, Simon

AU - Emery, Aidan M.

AU - The IAVI Protocol C Investigators & The IAVI African HIV Research Network

AU - Allen, Susan

AU - Kilembe, William

AU - Lakhi, Shabir

AU - Inambao, Mubiana

AU - Karita, Etienne

AU - Kamali, Anatoli

AU - Sanders, Eduard J.

AU - Anzala, Omu

AU - Edward, Vinodh

AU - Bekker, Linda-Gail

AU - Tang, Jianming

AU - Gilmour, Jill

AU - Hunter, Eric

AU - Price, Matt

AU - Landais, Elise

AU - Hokke, Cornelis H.

AU - Angulo, Jesus

AU - Reichardt, Niels

AU - Doores, Katie J.

PY - 2022/3/29

Y1 - 2022/3/29

N2 - The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.

AB - The HIV-1 Envelope glycoprotein (Env) is the sole target for broadly neutralizing antibodies (bnAbs). Env is heavily glycosylated with host-derived N-glycans, and many bnAbs bind to, or are dependent upon, Env glycans for neutralization. Although glycan-binding bnAbs are frequently detected in HIV-infected individuals, attempts to elicit them have been unsuccessful because of the poor immunogenicity of Env N-glycans. Here, we report cross-reactivity of glycan-binding bnAbs with self- and non-self N-glycans and glycoprotein antigens from different life-stages of Schistosoma mansoni. Using the IAVI Protocol C HIV infection cohort, we examine the relationship between S. mansoni seropositivity and development of bnAbs targeting glycan-dependent epitopes. We show that the unmutated common ancestor of the N332/V3-specific bnAb lineage PCDN76, isolated from an HIV-infected donor with S. mansoni seropositivity, binds to S. mansoni cercariae while lacking reactivity to gp120. Overall, these results present a strategy for elicitation of glycan-reactive bnAbs which could be exploited in HIV-1 vaccine development.

U2 - 10.1016/j.celrep.2022.110611

DO - 10.1016/j.celrep.2022.110611

M3 - Article

VL - 38

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 13

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ER -