کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10967453 | 1102831 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Elicitation of broadly reactive antibodies against glycan-modulated neutralizing V3 epitopes of HIV-1 by immune complex vaccines
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کلمات کلیدی
ABSNaSCNCD4BSDDAnAbsN-linked glycansMPLmAbsantibodies - آنتی بادی هاNeutralizing antibodies - آنتی بادیهای ناتریالSodium thiocyanate - تیتانیم سدیمV3 loop - حلقه V3Neutralization - خنثی سازیdimethyldioctadecylammonium bromide - دی متیل دیکتوسیدیل آمونیوم برومیدMonophosphoryl lipid A - لیپید مونوفسفریل Aimmune complex - مجتمع ایمنیVaccine - واکسنMonoclonal antibodies - پادتنهای تَکتیرهAntibody - پادتَن یا آنتیبادی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
HIV-1 envelope gp120 is the target for neutralizing antibodies (NAbs) against the virus. Various approaches have been explored to improve immunogenicity of broadly neutralizing epitopes on this antigen with limited success. We previously demonstrated that immunogenicity of gp120 and especially its V3 epitopes was enhanced when gp120 was co-administered as immune-complex vaccines with monoclonal antibodies (mAb) to the CD4-binding site (CD4bs). To define the mechanisms by which immune complexes influence V3 immunogenicity, we compared gp120 complexed with mAbs specific for the C2 region (1006-30), the V2 loop (2158), or the CD4bs (654), and found that the gp120/654 and gp120/2158 complexes elicited anti-V3 NAbs, but the gp120/654 complex was the most effective. gp120 complexed with 654 F(abâ²)2 was as potent, indicating that V3 immunogenicity is determined by the specificity of the mAb's Fab fragment used to form the complexes. Importantly, the gp120/654 complex not only induced anti-gp120 antibodies (Abs) to higher titers, but also of greater avidity. The Abs were cross-reactive with V3 peptides from most subtype B and some subtype C isolates. Neutralization was detected only against Tier-1 HIV-1 pseudoviruses, while Tier-2 viruses, including the homologous JRFL strain, were not neutralized. However, JRFL produced in the presence of a mannosidase inhibitor was sensitive to anti-V3 NAbs in the immune sera. These results demonstrate that the gp120/654 complex is a potent immunogen for eliciting cross-reactive functional NAbs against V3 epitopes, of which exposure is determined by the specific compositions of glycans shrouding the HIV-1 envelope glycoproteins.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 31, Issue 46, 4 November 2013, Pages 5413-5421
Journal: Vaccine - Volume 31, Issue 46, 4 November 2013, Pages 5413-5421
نویسندگان
Rajnish Kumar, Michael Tuen, Jianping Liu, Arthur NÃ das, Ruimin Pan, Xiangpeng Kong, Catarina E. Hioe,