Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Matthias G Pauthner; Joseph P Nkolola; Colin Havenar-Daughton; Ben Murrell; Samantha M Reiss; Raiza Bastidas; Jérémie Prévost; Rebecca Nedellec; Benjamin von Bredow; Peter Abbink; Christopher A Cottrell; Daniel W Kulp; Talar Tokatlian; Bartek Nogal; Matteo Bianchi; Hui Li; Jeong Hyun Lee; Salvatore T Butera; David T Evans; Lars Hangartner; Andrés Finzi; Ian A Wilson; Richard T Wyatt; Darrell J Irvine; William R Schief; Andrew B Ward; Rogier W Sanders; Shane Crotty; George M Shaw; Dan H Barouch; Dennis R Burton

doi:https://doi.org/10.1016/j.immuni.2018.11.011

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Matthias G Pauthner, Joseph P Nkolola, Colin Havenar-Daughton, Ben Murrell, Samantha M Reiss, Raiza Bastidas, Jérémie Prévost, Rebecca Nedellec, Benjamin von Bredow, Peter Abbink, Christopher A Cottrell, Daniel W Kulp, Talar Tokatlian, Bartek Nogal, Matteo Bianchi, Hui Li, Jeong Hyun Lee, Salvatore T Butera, David T Evans, Lars HangartnerAndrés Finzi, Ian A Wilson, Richard T Wyatt, Darrell J Irvine, William R Schief, Andrew B Ward, Rogier W Sanders, Shane Crotty, George M Shaw, Dan H Barouch, Dennis R Burton

Medical Microbiology and Infection Prevention (AMC)

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

114 Citations (Scopus)

Abstract

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

Original language	English
Pages (from-to)	241-252.e6
Journal	Immunity
Volume	50
Issue number	1
DOIs	https://doi.org/10.1016/j.immuni.2018.11.011
Publication status	Published - 15 Jan 2019

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https://doi.org/10.1016/j.immuni.2018.11.011

Cite this

Pauthner, M. G., Nkolola, J. P., Havenar-Daughton, C., Murrell, B., Reiss, S. M., Bastidas, R., Prévost, J., Nedellec, R., von Bredow, B., Abbink, P., Cottrell, C. A., Kulp, D. W., Tokatlian, T., Nogal, B., Bianchi, M., Li, H., Lee, J. H., Butera, S. T., Evans, D. T., ... Burton, D. R. (2019). Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers. Immunity, 50(1), 241-252.e6. https://doi.org/10.1016/j.immuni.2018.11.011

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title = "Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers",

abstract = "Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.",

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Pauthner, MG, Nkolola, JP, Havenar-Daughton, C, Murrell, B, Reiss, SM, Bastidas, R, Prévost, J, Nedellec, R, von Bredow, B, Abbink, P, Cottrell, CA, Kulp, DW, Tokatlian, T, Nogal, B, Bianchi, M, Li, H, Lee, JH, Butera, ST, Evans, DT, Hangartner, L, Finzi, A, Wilson, IA, Wyatt, RT, Irvine, DJ, Schief, WR, Ward, AB, Sanders, RW, Crotty, S, Shaw, GM, Barouch, DH & Burton, DR 2019, 'Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers', Immunity, vol. 50, no. 1, pp. 241-252.e6. https://doi.org/10.1016/j.immuni.2018.11.011

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AU - Pauthner, Matthias G

AU - Nkolola, Joseph P

AU - Havenar-Daughton, Colin

AU - Murrell, Ben

AU - Reiss, Samantha M

AU - Bastidas, Raiza

AU - Prévost, Jérémie

AU - Nedellec, Rebecca

AU - von Bredow, Benjamin

AU - Abbink, Peter

AU - Cottrell, Christopher A

AU - Kulp, Daniel W

AU - Tokatlian, Talar

AU - Nogal, Bartek

AU - Bianchi, Matteo

AU - Li, Hui

AU - Lee, Jeong Hyun

AU - Butera, Salvatore T

AU - Evans, David T

AU - Hangartner, Lars

AU - Finzi, Andrés

AU - Wilson, Ian A

AU - Wyatt, Richard T

AU - Irvine, Darrell J

AU - Schief, William R

AU - Ward, Andrew B

AU - Sanders, Rogier W

AU - Crotty, Shane

AU - Shaw, George M

AU - Barouch, Dan H

AU - Burton, Dennis R

PY - 2019/1/15

Y1 - 2019/1/15

N2 - Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

AB - Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIVBG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID50 nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

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DO - https://doi.org/10.1016/j.immuni.2018.11.011

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