Development of SHIVs for Vaccine Evaluation in NHP

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Experimental Simian Immunodeficiency Virus (SIV) infection of Asian macaques represents a preferred animal model for many AIDS related studies but is not ideal for evaluating certain candidate HIV vaccines, especially Env directed vaccines, because it is not possible to directly test protection against HIV challenge; HIV does not productively infect or cause disease in macaques. To address this problem many investigators have the constructed chimeric viruses designated Simian Human Immunodeficiency Viruses (SHIV), with genomes in which most or all of the SIV envelope sequence is replaced by the corresponding HIV envelope sequence, in a SIV backbone, resulting in viruses that have HIV envelope glycoproteins on their surface, but can infect macaque cells and macaques. While such viruses allow testing of the protective potential of HIV Env immunogens against acquisition of infection, the patterns of viral replication and pathogenesis in vivo in macaques for many of these viruses are not fully reflective of HIV biology and pathogenesis, limiting their utility for assessing interventions that modulate the course of infection or its consequences.

Generation of SHIVs that replicate robustly in macaques has proven difficult; available SHIVs have historically been limited in number and the HIV Env sequences incorporated have not always reflected those of greatest global interest for vaccine studies, namely CCR5-tropic, transmitted/founder Envs with a Tier 2 neutralization phenotype, particularly from Clade C viruses. While there has been some recent progress toward producing SHIVs with some of these desirable features, the confluence of sharply defined needs in the field with emerging new methods for generating and selecting useful SHIVs and producing challenge stocks for NHP vaccine studies suggests that a coordinated effort at this time to generate new SHIVs and associated characterized challenge stocks could greatly facilitate research progress, including evaluation and prioritization of HIV Env-containing candidate vaccines.

This workshop is intended to bring together leading investigators working on the generation and characterization of new SHIVs and investigators working on vaccines and mAbs whose work would benefit from the availability of such challenge viruses, in order to facilitate the coordination and support of research efforts in this area.

Objectives and deliverables
Review and summarize the following topics, focusing specifically on HIV Env-carrying SIV chimeras

  • Potential uses of SHIVs in HIV vaccine research and desiderata for each application
  • Review currently available SHIVs: diversity of represented HIV sequences and in vitro, in vivo properties
  • Status update on ongoing efforts and approaches to create and evaluate additional viruses
  • Remaining gaps and needs
  • Current approaches to challenge stock production and characterization
  • Potential funding and collaborative approaches to facilitate progress in this area

Alan Schultz, Division of AIDS, NIAID
Jeffrey Lifson, Frederick National Laboratory
Yegor Voronin, Global HIV Vaccine Enterprise

Meeting details
Format: One-day think tank bringing together 25-30 people.
Date: Thursday March 17, 2016
Location: New York, NY

Attendance is by invitation only. If you would like to attend the meeting, please contact Yegor Voronin at [email protected]

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