Abstract

Methods Receptor usage was assessed using CD46 transgenic mouse cells, as well as by CARand CD46-specific mAb blocking studies using human PBMC. Twelve adult rhesus monkeys were inoculated with of 10 viral particles (vp) of replication-competent Ad5 and Ad26 (N=6) or saline (N=6) at weeks -8 and -4, and were vaccinated intramuscularly with 3×10 vp replication-incompetent Ad26-Gag/Pol/Env vectors. At week 2, monkeys were sacrificed to assess immunologic and inflammatory responses at mucosal surfaces.

Highlights

  • Adenovirus serotype 5 (Ad5) utilizes coxsackievirus and adenovirus receptor (CAR) as its primary cellular receptor

  • Transduction by Ad26 and Ad35 vectors was markedly enhanced in CD46 transgenic mouse cells compared with wild type mouse cells

  • Transduction of human PBMC by Ad26 and Ad35 vectors was efficiently blocked by the anti-CD46 mAbs 13/42, M177 and MEM-258, but not by the anti-CAR mAbs RmcB and E1-1

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Summary

Introduction

Adenovirus serotype 5 (Ad5) utilizes coxsackievirus and adenovirus receptor (CAR) as its primary cellular receptor. Adenovirus serotype 26 utilizes CD46 as primary cellular receptor and only transiently activates T lymphocytes following vaccination of rhesus monkeys H Li1*, EG Rhee1, K Masek-Hammerman2, JE Teigler1, P Abbink1, DH Barouch1

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