Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.
Comparative immunogenicity of HIV-1 clade C envelope proteins for prime/boost studies.
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DOI：
10.1371/journal.pone.0012076
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发表时间：
2010-08-11
期刊：
影响因子：
3.7
通讯作者：
Berman PW
中科院分区：
文献类型：
--
作者：
Smith DH;Winters-Digiacinto P;Mitiku M;O'Rourke S;Sinangil F;Wrin T;Montefiori DC;Berman PW
先前的临床疗效试验未能支持继续开发重组gp120 （rgp120）作为HIV候选疫苗。然而，最近在泰国进行的RV144艾滋病毒疫苗试验表明，先用金丝猴痘vCP1521接种，再用rgp120接种，这一初始/增强免疫策略可以提供显著的（尽管是适度的）艾滋病毒感染保护。基于这些结果，人们对开发基于rgp120的抗原进行后续疫苗试验重新产生了兴趣，这种免疫方法可以应用于其他艾滋病毒感染高风险人群。特别令人感兴趣的是非洲、印度和中国的C支病毒感染者。在293细胞中表达了10个进化支C rgp120包膜蛋白，通过免疫亲和层析纯化，用于免疫豚鼠。收集得到的血清并在棋盘实验中分析rgp120结合、V3肽结合和CD4阻断活性。病毒中和研究采用两种不同的测定方法和两种不同的C支病毒组进行。对C支和B支病毒及病毒蛋白具有高度的交叉反应性。大多数（但不是全部）免疫原检测产生的抗体能中和1级进化支B病毒，一些血清能中和多种进化支C病毒。与其他抗原相比，用CN97001 HIV毒株的rgp120免疫似乎能引起更高的交叉中和抗体滴度。虽然所有测试的进化支C抗原都是免疫原性的，但有些抗原在激发病毒中和抗体方面比其他抗原更有效。中和滴度与rgp120结合、V3肽结合或CD4阻断活性无关。CN97001 rgp120引发了最高水平的中和抗体，应考虑用于进一步的HIV疫苗开发研究。
Previous clinical efficacy trials failed to support the continued development of recombinant gp120 (rgp120) as a candidate HIV vaccine. However, the recent RV144 HIV vaccine trial in Thailand showed that a prime/boost immunization strategy involving priming with canarypox vCP1521 followed by boosting with rgp120 could provide significant, although modest, protection from HIV infection. Based on these results, there is renewed interest in the development of rgp120 based antigens for follow up vaccine trials, where this immunization approach can be applied to other cohorts at high risk for HIV infection. Of particular interest are cohorts in Africa, India, and China that are infected with clade C viruses. A panel of 10 clade C rgp120 envelope proteins was expressed in 293 cells, purified by immunoaffinity chromatography, and used to immunize guinea pigs. The resulting sera were collected and analyzed in checkerboard experiments for rgp120 binding, V3 peptide binding, and CD4 blocking activity. Virus neutralization studies were carried out with two different assays and two different panels of clade C viruses. A high degree of cross reactivity against clade C and clade B viruses and viral proteins was observed. Most, but not all of the immunogens tested elicited antibodies that neutralized tier 1 clade B viruses, and some sera neutralized multiple clade C viruses. Immunization with rgp120 from the CN97001 strain of HIV appeared to elicit higher cross neutralizing antibody titers than the other antigens tested. While all of the clade C antigens tested were immunogenic, some were more effective than others in eliciting virus neutralizing antibodies. Neutralization titers did not correlate with rgp120 binding, V3 peptide binding, or CD4 blocking activity. CN97001 rgp120 elicited the highest level of neutralizing antibodies, and should be considered for further HIV vaccine development studies.
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DOI：
10.1097/01.qai.0000136091.72955.4b
发表时间：
2004-09-01
影响因子：
3.6
作者：
Pitisuttithum, P;Berman, PW;Francis, DP
通讯作者：
Francis, DP
影响因子：
1.5
作者：
POWELL, MF;EASTMAN, DJ;BERMAN, PW
通讯作者：
BERMAN, PW
影响因子：
5.4
作者：
Nkolola, Joseph P.;Peng, Hanqin;Barouch, Dan H.
通讯作者：
Barouch, Dan H.
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
影响因子：
56.9
作者：
LASKY, LA;GROOPMAN, JE;BERMAN, PW
通讯作者：
BERMAN, PW