Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Syna Kuriakose Gift; Lindsay Wieczorek; Eric Sanders-Buell; Michelle Zemil; Sebastian Molnar; Gina Donofrio; Samantha Townsley; Agnes L. Chenine; Meera Bose; Hung V. Trinh; Brittani M. Barrows; Somchai Sriplienchan; Suchai Kitsiripornchai; Sorachai Nitayapan; Leigh Anne Eller; Mangala Rao; Guido Ferrari; Nelson L. Michael; Julie A. Ake; Shelly J. Krebs; Merlin L. Robb; Sodsai Tovanabutra; Victoria R. Polonis

doi:10.1128/jvi.01635-22

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Syna Kuriakose Gift, Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Sebastian Molnar, Gina Donofrio, Samantha Townsley, Agnes L. Chenine, Meera Bose, Hung V. Trinh, Brittani M. Barrows, Somchai Sriplienchan, Suchai Kitsiripornchai, Sorachai Nitayapan, Leigh Anne Eller, Mangala Rao, Guido Ferrari, Nelson L. Michael, Julie A. Ake, Shelly J. KrebsMerlin L. Robb, Sodsai Tovanabutra, Victoria R. Polonis^*

^*Corresponding author for this work

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

4 Scopus citations

Abstract

Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC₅₀] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection.

Original language	English
Journal	Journal of Virology
Volume	97
Issue number	2
DOIs	https://doi.org/10.1128/jvi.01635-22
State	Published - Feb 2023
Externally published	Yes

Keywords

ADCC
CRF01_AE
HIV-1
V1V2
autologous neutralization
neutralization breadth
viral load set point

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10.1128/jvi.01635-22

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Gift, S. K., Wieczorek, L., Sanders-Buell, E., Zemil, M., Molnar, S., Donofrio, G., Townsley, S., Chenine, A. L., Bose, M., Trinh, H. V., Barrows, B. M., Sriplienchan, S., Kitsiripornchai, S., Nitayapan, S., Eller, L. A., Rao, M., Ferrari, G., Michael, N. L., Ake, J. A., ... Polonis, V. R. (2023). Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies. Journal of Virology, 97(2). https://doi.org/10.1128/jvi.01635-22

@article{93fa7fb3ebbc4da0a38829b183df9245,

title = "Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies",

abstract = "Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection.",

keywords = "ADCC, CRF01_AE, HIV-1, V1V2, autologous neutralization, neutralization breadth, viral load set point",

author = "Gift, {Syna Kuriakose} and Lindsay Wieczorek and Eric Sanders-Buell and Michelle Zemil and Sebastian Molnar and Gina Donofrio and Samantha Townsley and Chenine, {Agnes L.} and Meera Bose and Trinh, {Hung V.} and Barrows, {Brittani M.} and Somchai Sriplienchan and Suchai Kitsiripornchai and Sorachai Nitayapan and Eller, {Leigh Anne} and Mangala Rao and Guido Ferrari and Michael, {Nelson L.} and Ake, {Julie A.} and Krebs, {Shelly J.} and Robb, {Merlin L.} and Sodsai Tovanabutra and Polonis, {Victoria R.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Kuriakose Gift et al.",

year = "2023",

month = feb,

doi = "10.1128/jvi.01635-22",

language = "English",

volume = "97",

journal = "Journal of Virology",

issn = "0022-538X",

number = "2",

}

Gift, SK, Wieczorek, L, Sanders-Buell, E, Zemil, M, Molnar, S, Donofrio, G, Townsley, S, Chenine, AL, Bose, M, Trinh, HV, Barrows, BM, Sriplienchan, S, Kitsiripornchai, S, Nitayapan, S, Eller, LA, Rao, M, Ferrari, G, Michael, NL , Ake, JA, Krebs, SJ, Robb, ML, Tovanabutra, S & Polonis, VR 2023, 'Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies', Journal of Virology, vol. 97, no. 2. https://doi.org/10.1128/jvi.01635-22

TY - JOUR

T1 - Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection

T2 - Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

AU - Gift, Syna Kuriakose

AU - Wieczorek, Lindsay

AU - Sanders-Buell, Eric

AU - Zemil, Michelle

AU - Molnar, Sebastian

AU - Donofrio, Gina

AU - Townsley, Samantha

AU - Chenine, Agnes L.

AU - Bose, Meera

AU - Trinh, Hung V.

AU - Barrows, Brittani M.

AU - Sriplienchan, Somchai

AU - Kitsiripornchai, Suchai

AU - Nitayapan, Sorachai

AU - Eller, Leigh Anne

AU - Rao, Mangala

AU - Ferrari, Guido

AU - Michael, Nelson L.

AU - Ake, Julie A.

AU - Krebs, Shelly J.

AU - Robb, Merlin L.

AU - Tovanabutra, Sodsai

AU - Polonis, Victoria R.

PY - 2023/2

Y1 - 2023/2

N2 - Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection.

AB - Understanding the dynamics of early immune responses to HIV-1 infection, including the evolution of initial neutralizing and antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, will inform HIV vaccine design. In this study, we assess the development of autologous neutralizing antibodies (ANAbs) against founder envelopes (Envs) from 18 participants with HIV-1 CRF01_AE acute infection. The timing of ANAb development directly associated with the magnitude of the longitudinal ANAb response. Participants that developed ANAbs within 6 months of infection had significantly higher ANAb responses at 1 year (50% inhibitory concentration [IC50] geometric mean titer [GMT] = 2,010 versus 184; P = 0.001) and 2 years (GMT = 3,479 versus 340; P = 0.015), compared to participants that developed ANAb responses after 6 months. Participants with later development of ANAb tended to develop an earlier, potent heterologous tier 1 (92TH023) neutralizing antibody (NAb) response (P = 0.049). CRF01_AE founder Env V1V2 loop lengths correlated indirectly with the timing (P = 0.002, r = 20.675) and directly with magnitude (P = 0.005, r = 0.635) of ANAb responses; Envs with longer V1V2 loop lengths elicited earlier and more potent ANAb responses. While ANAb responses did not associate with viral load, the viral load set point correlated directly with neutralization of the heterologous 92TH023 strain (P = 0.007, r = 0.638). In contrast, a striking inverse correlation was observed between viral load set point and peak ADCC against heterologous 92TH023 Env strain (P = 0.0005, r = 20.738). These data indicate that specific antibody functions can be differentially related to viral load set point and may affect HIV-1 pathogenesis. Exploiting Env properties, such as V1V2 length, could facilitate development of subtype-specific vaccines that elicit more effective immune responses and improved protection.

KW - ADCC

KW - CRF01_AE

KW - HIV-1

KW - V1V2

KW - autologous neutralization

KW - neutralization breadth

KW - viral load set point

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U2 - 10.1128/jvi.01635-22

DO - 10.1128/jvi.01635-22

M3 - Article

C2 - 36749076

AN - SCOPUS:85149203848

SN - 0022-538X

VL - 97

JO - Journal of Virology

JF - Journal of Virology

IS - 2

ER -

Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

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Keywords

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