Abstract

Background Infection of macaques with chimeric Simian/Human Immunodeficiency Viruses (SHIVs) provides a powerful model for HIV pathogenesis and vaccine development. A limitation of the SHIVs routinely used for vaccine studies, e.g. SHIV-1157ipd3N4, SHIV-SF162P3, and SHIV-BaL, is that they don’t express quaternary neutralization epitopes (QNEs) that are targets of broadly neutralizing antibodies like PG9, PG16, and CAP256 sera. We sought to introduce the QNEs into functional SHIVs to study how such antibodies develop during infection and help guide the creation of antigens capable of eliciting such antibodies.

Highlights

  • Infection of macaques with chimeric Simian/Human Immunodeficiency Viruses (SHIVs) provides a powerful model for HIV pathogenesis and vaccine development

  • A limitation of the SHIVs routinely used for vaccine studies, e.g. SHIV-1157ipd3N4, SHIV-SF162P3, and SHIV-BaL, is that they don’t express quaternary neutralization epitopes (QNEs) that are targets of broadly neutralizing antibodies like PG9, PG16, and CAP256 sera

  • Full-length SHIVs expressing the mutant Envs were tested for growth in PBMCs, and high titre stocks from those that grew were used to infect pigtail macaques

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Summary

Introduction

Infection of macaques with chimeric Simian/Human Immunodeficiency Viruses (SHIVs) provides a powerful model for HIV pathogenesis and vaccine development. A limitation of the SHIVs routinely used for vaccine studies, e.g. SHIV-1157ipd3N4, SHIV-SF162P3, and SHIV-BaL, is that they don’t express quaternary neutralization epitopes (QNEs) that are targets of broadly neutralizing antibodies like PG9, PG16, and CAP256 sera. We sought to introduce the QNEs into functional SHIVs to study how such antibodies develop during infection and help guide the creation of antigens capable of eliciting such antibodies

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