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Limitations of the Human‐PBL‐SCID Mouse Model for Vaginal Transmission of HIV‐1
Author(s) -
D'Cruz Osmond J.,
Uckun Fatih M.
Publication year - 2007
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2007.00478.x
Subject(s) - spleen , immunology , vaginal microbicide , semen , microbicide , viral load , vagina , medicine , biology , andrology , virology , human immunodeficiency virus (hiv) , population , microbicides for sexually transmitted diseases , surgery , environmental health , health services
Problem SCID mice reconstituted with human peripheral blood lymphocytes (PBL) are amenable to vaginal transmission of HIV‐1. We investigated the effectiveness of this model to establish systemic HIV‐1 infection. Method of study Eighty progesterone‐primed C.B‐17 SCID mice were reconstituted with human‐PBLs and intravaginally inoculated with CCR5 HIV‐1 (BaL or 92BR09) infected human‐PBLs in the presence of human semen. After two weeks, viral RNA load in spleen, peritoneal lavage (PL), and serum was quantitated by the nucleic acid sequence‐based amplification method. Results In five independent experiments, spleen from 8/60 (13.3%), PL from 7/60 (11.6%), and serum from 16/56 (28.5%) mice were positive for BaL HIV‐1 infection. Similarly, spleen from 4/20 (20%), PL from 1/20 (5%) and serum from 5/20 (25%) mice vaginally inoculated with 92BR09‐infected human‐PBLs were positive for HIV‐1. A one‐sided power analysis using normal approximation revealed that at 5% significance level, the overall response rate need to increase form 0.29 to 0.9 and 80% of the control groups needs to achieve a response rate between 6/10 and 9/10 to make the assay feasible. Conclusion The incidence of vaginal transmission of CCR5 HIV‐1 in the human‐PBL‐SCID mouse was low and variable, which constitutes a major disadvantage for preclinical evaluation of vaginal microbicides.