Enhanced in vitro transcytosis of simian immunodeficiency virus mediated by vaccine-induced antibody predicts transmitted/founder strain number after rectal challenge.
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.
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine.
Sandeep
S
Gupta
Animal Models and Retroviral Vaccine Section.
Poonam
P
Pegu
Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
David J
DJ
Venzon
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine.
Johannes S
JS
Gach
Center for Comparative Medicine.
Zhong-Min
ZM
Ma
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine.
Gary
G
Landucci
Center for Comparative Medicine Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis.
Christopher J
CJ
Miller
Animal Models and Retroviral Vaccine Section.
Genoveffa
G
Franchini
Division of Infectious Diseases, Department of Medicine, University of California, Irvine School of Medicine, Irvine.
Donald N
DN
Forthal
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D045744:Cell Line, Tumor; D016889:Endometrial Neoplasms / Q000276:immunology / Q000821:virology; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D011961:Receptors, Fc / Q000276:immunology; D012007:Rectum / Q000276:immunology* / Q000821:virology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D057900:Transcytosis; D014765:Viral Vaccines / Q000276:immunology*
D000906:Antibodies; D015395:Histocompatibility Antigens Class I; D011961:Receptors, Fc; D014765:Viral Vaccines; C100688:Fc receptor, neonatal
Fc neonatal receptor; SIV; antibody; transcytosis; vaccine