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

Non-neutralizing Antibodies Alter the Course of HIV-1 Infection In Vivo.
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Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AAK, Lorenzi JCC, Nogueira L, Golijanin J, Scheid JF, Seaman MS, Gazumyan A, Zolla-Pazner S, Nussenzweig MC,


Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AAK, Lorenzi JCC, Nogueira L, Golijanin J, Scheid JF, Seaman MS, Gazumyan A, Zolla-Pazner S, Nussenzweig MC, (click to view)

Horwitz JA, Bar-On Y, Lu CL, Fera D, Lockhart AAK, Lorenzi JCC, Nogueira L, Golijanin J, Scheid JF, Seaman MS, Gazumyan A, Zolla-Pazner S, Nussenzweig MC,

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Cell 2017 07 27170(4) 637-648.e10 pii 10.1016/j.cell.2017.06.048

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. PAPERCLIP.

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