Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Jon M. Steichen; Ivy Phung; Eugenia Salcedo; Gabriel Ozorowski; Jordan R. Willis; Sabyasachi Baboo; Alessia Liguori; Christopher A. Cottrell; Jonathan L. Torres; Patrick J. Madden; Krystal M. Ma; Henry J. Sutton; Jeong Hyun Lee; Oleksandr Kalyuzhniy; Joel D. Allen; Oscar L. Rodriguez; Yumiko Adachi; Tina Marie Mullen; Erik Georgeson; Michael Kubitz; Alison Burns; Shawn Barman; Rohini Mopuri; Amanda Metz; Tasha K. Altheide; Jolene K. Diedrich; Swati Saha; Kaitlyn Shields; Steven E. Schultze; Melissa L. Smith; Torben Schiffner; Dennis R. Burton; Corey T. Watson; Steven E. Bosinger; Max Crispin; John R. Yates; James C. Paulson; Andrew B. Ward; Devin Sok; Shane Crotty; William R. Schief

doi:10.1126/science.adj8321

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Jon M. Steichen, Ivy Phung, Eugenia Salcedo, Gabriel Ozorowski, Jordan R. Willis, Sabyasachi Baboo, Alessia Liguori, Christopher A. Cottrell, Jonathan L. Torres, Patrick J. Madden, Krystal M. Ma, Henry J. Sutton, Jeong Hyun Lee, Oleksandr Kalyuzhniy, Joel D. Allen, Oscar L. Rodriguez, Yumiko Adachi, Tina Marie Mullen, Erik Georgeson, Michael KubitzAlison Burns, Shawn Barman, Rohini Mopuri, Amanda Metz, Tasha K. Altheide, Jolene K. Diedrich, Swati Saha, Kaitlyn Shields, Steven E. Schultze, Melissa L. Smith, Torben Schiffner, Dennis R. Burton, Corey T. Watson, Steven E. Bosinger, Max Crispin, John R. Yates, James C. Paulson, Andrew B. Ward, Devin Sok, Shane Crotty, William R. Schief

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

8 Scopus citations

Abstract

Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

Original language	English
Pages (from-to)	754-756
Number of pages	3
Journal	Science
Volume	384
Issue number	6697
DOIs	https://doi.org/10.1126/science.adj8321
State	Published - 17 May 2024
Externally published	Yes

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Steichen, J. M., Phung, I., Salcedo, E., Ozorowski, G., Willis, J. R., Baboo, S., Liguori, A., Cottrell, C. A., Torres, J. L., Madden, P. J., Ma, K. M., Sutton, H. J., Lee, J. H., Kalyuzhniy, O., Allen, J. D., Rodriguez, O. L., Adachi, Y., Mullen, T. M., Georgeson, E., ... Schief, W. R. (2024). Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates. Science, 384(6697), 754-756. https://doi.org/10.1126/science.adj8321

@article{a90bc86cd0e7479ea240e9498f7ca03f,

title = "Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates",

abstract = "Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.",

author = "Steichen, {Jon M.} and Ivy Phung and Eugenia Salcedo and Gabriel Ozorowski and Willis, {Jordan R.} and Sabyasachi Baboo and Alessia Liguori and Cottrell, {Christopher A.} and Torres, {Jonathan L.} and Madden, {Patrick J.} and Ma, {Krystal M.} and Sutton, {Henry J.} and Lee, {Jeong Hyun} and Oleksandr Kalyuzhniy and Allen, {Joel D.} and Rodriguez, {Oscar L.} and Yumiko Adachi and Mullen, {Tina Marie} and Erik Georgeson and Michael Kubitz and Alison Burns and Shawn Barman and Rohini Mopuri and Amanda Metz and Altheide, {Tasha K.} and Diedrich, {Jolene K.} and Swati Saha and Kaitlyn Shields and Schultze, {Steven E.} and Smith, {Melissa L.} and Torben Schiffner and Burton, {Dennis R.} and Watson, {Corey T.} and Bosinger, {Steven E.} and Max Crispin and Yates, {John R.} and Paulson, {James C.} and Ward, {Andrew B.} and Devin Sok and Shane Crotty and Schief, {William R.}",

year = "2024",

month = may,

day = "17",

doi = "10.1126/science.adj8321",

language = "English",

volume = "384",

pages = "754--756",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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Steichen, JM, Phung, I, Salcedo, E, Ozorowski, G, Willis, JR, Baboo, S, Liguori, A, Cottrell, CA, Torres, JL, Madden, PJ, Ma, KM, Sutton, HJ, Lee, JH, Kalyuzhniy, O, Allen, JD, Rodriguez, OL, Adachi, Y, Mullen, TM, Georgeson, E, Kubitz, M, Burns, A, Barman, S, Mopuri, R, Metz, A, Altheide, TK, Diedrich, JK, Saha, S, Shields, K, Schultze, SE, Smith, ML, Schiffner, T, Burton, DR, Watson, CT, Bosinger, SE, Crispin, M, Yates, JR, Paulson, JC, Ward, AB, Sok, D, Crotty, S & Schief, WR 2024, 'Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates', Science, vol. 384, no. 6697, pp. 754-756. https://doi.org/10.1126/science.adj8321

TY - JOUR

T1 - Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

AU - Steichen, Jon M.

AU - Phung, Ivy

AU - Salcedo, Eugenia

AU - Ozorowski, Gabriel

AU - Willis, Jordan R.

AU - Baboo, Sabyasachi

AU - Liguori, Alessia

AU - Cottrell, Christopher A.

AU - Torres, Jonathan L.

AU - Madden, Patrick J.

AU - Ma, Krystal M.

AU - Sutton, Henry J.

AU - Lee, Jeong Hyun

AU - Kalyuzhniy, Oleksandr

AU - Allen, Joel D.

AU - Rodriguez, Oscar L.

AU - Adachi, Yumiko

AU - Mullen, Tina Marie

AU - Georgeson, Erik

AU - Kubitz, Michael

AU - Burns, Alison

AU - Barman, Shawn

AU - Mopuri, Rohini

AU - Metz, Amanda

AU - Altheide, Tasha K.

AU - Diedrich, Jolene K.

AU - Saha, Swati

AU - Shields, Kaitlyn

AU - Schultze, Steven E.

AU - Smith, Melissa L.

AU - Schiffner, Torben

AU - Burton, Dennis R.

AU - Watson, Corey T.

AU - Bosinger, Steven E.

AU - Crispin, Max

AU - Yates, John R.

AU - Paulson, James C.

AU - Ward, Andrew B.

AU - Sok, Devin

AU - Crotty, Shane

AU - Schief, William R.

PY - 2024/5/17

Y1 - 2024/5/17

N2 - Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

AB - Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, and vaccine priming of HCDR3-dominant bnAbs by germline-targeting immunogens has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in eight of eight rhesus macaques to substantial frequencies and with diverse lineages in germinal center and memory B cells. We confirmed bnAb-mimicking, HCDR3-dominant, trimer-binding interactions with cryo-electron microscopy. Our results demonstrate proof of principle for HCDR3-dominant bnAb-precursor priming in outbred animals and suggest that N332-GT5 holds promise for the induction of similar responses in humans.

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U2 - 10.1126/science.adj8321

DO - 10.1126/science.adj8321

M3 - Article

C2 - 38753769

AN - SCOPUS:85193492583

SN - 0036-8075

VL - 384

SP - 754

EP - 756

JO - Science

JF - Science

IS - 6697

ER -

Vaccine priming of rare HIV broadly neutralizing antibody precursors in nonhuman primates

Abstract

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