Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo

Joshua A. Horwitz; Yotam Bar-On; Ching Lan Lu; Daniela Fera; Ainsley A.K. Lockhart; Julio C.C. Lorenzi; Lilian Nogueira; Jovana Golijanin; Johannes F. Scheid; Michael S. Seaman; Anna Gazumyan; Susan Zolla-Pazner; Michel C. Nussenzweig

doi:10.1016/j.cell.2017.06.048

Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo

Joshua A. Horwitz, Yotam Bar-On, Ching Lan Lu, Daniela Fera, Ainsley A.K. Lockhart, Julio C.C. Lorenzi, Lilian Nogueira, Jovana Golijanin, Johannes F. Scheid, Michael S. Seaman, Anna Gazumyan, Susan Zolla-Pazner, Michel C. Nussenzweig

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113 Scopus citations

Abstract

Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo.

Original language	English
Pages (from-to)	637-648.e10
Journal	Cell
Volume	170
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2017.06.048
State	Published - 10 Aug 2017

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title = "Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo",

abstract = "Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo.",

author = "Horwitz, {Joshua A.} and Yotam Bar-On and Lu, {Ching Lan} and Daniela Fera and Lockhart, {Ainsley A.K.} and Lorenzi, {Julio C.C.} and Lilian Nogueira and Jovana Golijanin and Scheid, {Johannes F.} and Seaman, {Michael S.} and Anna Gazumyan and Susan Zolla-Pazner and Nussenzweig, {Michel C.}",

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doi = "10.1016/j.cell.2017.06.048",

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AU - Horwitz, Joshua A.

AU - Bar-On, Yotam

AU - Lu, Ching Lan

AU - Fera, Daniela

AU - Lockhart, Ainsley A.K.

AU - Lorenzi, Julio C.C.

AU - Nogueira, Lilian

AU - Golijanin, Jovana

AU - Scheid, Johannes F.

AU - Seaman, Michael S.

AU - Gazumyan, Anna

AU - Zolla-Pazner, Susan

AU - Nussenzweig, Michel C.

PY - 2017/8/10

Y1 - 2017/8/10

N2 - Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo.

AB - Non-neutralizing antibodies (nnAbs) to HIV-1 show little measurable activity in prevention or therapy in animal models yet were the only correlate of protection in the RV144 vaccine trial. To investigate the role of nnAbs on HIV-1 infection in vivo, we devised a replication-competent HIV-1 reporter virus that expresses a heterologous HA-tag on the surface of infected cells and virions. Anti-HA antibodies bind to, but do not neutralize, the reporter virus in vitro. However, anti-HA protects against infection in humanized mice and strongly selects for nnAb-resistant viruses in an entirely Fc-dependent manner. Similar results were also obtained with tier 2 HIV-1 viruses using a human anti-gp41 nnAb, 246D. While nnAbs are demonstrably less effective than broadly neutralizing antibodies (bNAbs) against HIV-1 in vitro and in vivo, the data show that nnAbs can protect against and alter the course of HIV-1 infection in vivo.

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JO - Cell

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Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo

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