Efficient Repeated Low-Dose Intravaginal Infection with SHIVSF162p3 in Chinese-Origin Rhesus Macaques
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1. Key Laboratory of Human Diseases Comparative Medicine,Ministry of Health; Institute of Medical Laboratory Animal Science,Chinese Academy of Medical Sciences; Key Laboratory of Human Diseases Animal Models,State Administration of Traditional Chinese Medicine,Beijing 100021,China;2. Mymetics Corporation,CH 1066 Epalinges,Switzerland

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    Abstract:

    Objective Nonhuman primate models are increasingly used in the screening of candidate AIDS vaccines and immunization strategies for advancement to large-scale human trials. The predictive value of such macaque studies is largely dependent upon the fidelity of the model system in mimicking human immunodeficiency virustype 1 ( HIV-1) infection in terms of viral transmission,replication,and pathogenesis. The aim of this study was to establish a Chineseorigin rhesus monkey model of CCR5-specific chimeric simian / human immunodeficiency virus ( SHIVSF162p3 ) infection,induced by repeated low-dose intravaginal infection,and explore whether this new chimeric model could be more efficient in AIDS vaccine research. Methods Totally 6 female Chinese-origin rhesus monkeys were enrolled in this study. All animals were intra-vaginally challenged 13 times with 1 mL of a phosphate buffered virus solution containing the heterologous SHIVSF162p3,with 20 TCID50 for the first 7 challenges and 30 TCID50 for the remaining 6 challenges. Challenges were done every 4-7 days. Whole blood was collected and plasma virus was quantified by real-time SYBR green RT-PCR and T cell subsets were determined by flow cytometry analysis. Results Systemtic infection was successfully established in 6 Chinese-origin rhesus macaques after 13 challenges. The peak of viral loads was between 106 copies/mL to 108 copies/mL,wherease their CD4 + /CD8 + ratio was decreased. Conclusions The results of this study provide a firm basis for establishing a Chinese rhesus macaques model of SHIV infection by repeated low dose of SHIVSF162p3,a route more close to natural way of AIDS infection. This model would be very useful for HIV-1 subtype B vaccine and pathogenesis studies.

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History
  • Received:October 08,2010
  • Revised:
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  • Online: November 11,2025
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