Enhanced in vitro transcytosis of simian immunodeficiency virus mediated by vaccine-induced antibody predicts transmitted/founder strain number after rectal challenge

Sandeep Gupta, Poonam Pegu, David J. Venzon, Johannes S. Gach, Zhong Min Ma, Gary Landucci, Chris J Miller, Genoveffa Franchini, Donald N. Forthal

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Background. The time to acquisition of simian immunodeficiency virus (SIV) infection following low-dose repeated rectal challenge correlated inversely with the number of transmitted/founder strains among macaques vaccinated with ALVAC-SIV/gp120 or gp120 alone. We determined if the ability of postvaccination, prechallenge sera to enhance SIVmac251 transcytosis across epithelial cells was associated with transmitted/founder strain number. Methods.Transcytosis was carried out by exposing sera and SIVmac251 to the apical surface of human endometrial carcinoma (HEC-1A) cells at pH 6.0 and 12 hours later quantifying virus in fluid bathing the basolateral cell surface (maintained at pH 7.4). These conditions allow Fc neonatal receptor (FcRn)-dependent shuttling of virus across cells. Results.There was a strong correlation between the amount of virus transcytosed and number of transmitted variants (R = 0.86, P <. 0001). We also found that 4 animals who remained uninfected after repeated rectal challenges had lower serum transcytosis activity than did 19 animals who subsequently became infected (P =. 003). Using immunohistochemistry, we demonstrated FcRn on columnar epithelial cells facing the lumen of the macaque rectum. Conclusions.Vaccine-induced antibody capable of enhancing transcytosis in vitro via FcRn may play a role in determining transmitted/founder strain number and infection outcomes following in vivo challenge.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalJournal of Infectious Diseases
Volume211
Issue number1
DOIs
StatePublished - Jan 1 2015

Keywords

  • antibody
  • Fc neonatal receptor
  • SIV
  • transcytosis
  • vaccine

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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