دورية أكاديمية
Delayed vaginal SHIV infection in VRC01 and anti-α4β7 treated rhesus macaques.
العنوان: | Delayed vaginal SHIV infection in VRC01 and anti-α4β7 treated rhesus macaques. |
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المؤلفون: | Giulia Calenda, Ines Frank, Géraldine Arrode-Brusés, Amarendra Pegu, Keyun Wang, James Arthos, Claudia Cicala, Kenneth A Rogers, Lisa Shirreff, Brooke Grasperge, James L Blanchard, Stephanie Maldonado, Kevin Roberts, Agegnehu Gettie, Francois Villinger, Anthony S Fauci, John R Mascola, Elena Martinelli |
المصدر: | PLoS Pathogens, Vol 15, Iss 5, p e1007776 (2019) |
بيانات النشر: | Public Library of Science (PLoS), 2019. |
سنة النشر: | 2019 |
المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
الوصف: | VRC01 protects macaques from vaginal SHIV infection after a single high-dose challenge. Infusion of a simianized anti-α4β7 mAb (Rh-α4β7) just prior to, and during repeated vaginal exposures to SIVmac251 partially protected macaques from vaginal SIV infection and rescued CD4+ T cells. To investigate the impact of combining VRC01 and Rh-α4β7 on SHIV infection, 3 groups of macaques were treated with a suboptimal dosing of VRC01 alone or in combination with Rh-α4β7 or with control antibodies prior to the initiation of weekly vaginal exposures to a high dose (1000 TCID50) of SHIVAD8-EO. The combination Rh-α4β7-VRC01 significantly delayed SHIVAD8-EO vaginal infection. Following infection, VRC01-Rh-α4β7-treated macaques maintained higher CD4+ T cell counts and exhibited lower rectal SIV-DNA loads compared to controls. Interestingly, VRC01-Rh-α4β7-treated macaques had fewer IL-17-producing cells in the blood and the gut during the acute phase of infection. Moreover, higher T cell responses to the V2-loop of the SHIVAD8-EO envelope in the VRC01-Rh-α4β7 group inversely correlated with set point viremia. The combination of suboptimal amounts of VRC01 and Rh-α4β7 delayed infection, altered antiviral immune responses and minimized CD4+ T cell loss. Further exploration of the effect of combining bNAbs with Rh-α4β7 on SIV/HIV infection and antiviral immune responses is warranted and may lead to novel preventive and therapeutic strategies. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1553-7366 1553-7374 |
Relation: | https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
DOI: | 10.1371/journal.ppat.1007776 |
URL الوصول: | https://doaj.org/article/56f99e9871a14c77a113d5c201dca31e |
رقم الأكسشن: | edsdoj.56f99e9871a14c77a113d5c201dca31e |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 15537366 15537374 |
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DOI: | 10.1371/journal.ppat.1007776 |