Deglycosylation of HIV-1 AE Gp140 Enhances the Capacity to Elicit Neutralizing Antibodies Against the Heterologous HIV-1 Clade

被引:6
作者
Zhang, Congyou [1 ,2 ]
Wan, Yanmin [1 ]
Shi, Jijing
Zhou, Mingzhe [1 ]
Meng, Zhefeng [3 ]
Yuan, Songhua [1 ]
Qiu, Chao [3 ]
Zhang, Xiaoyan [1 ,3 ]
Xu, Xuemei [2 ]
Liu, Chaoqi
Xu, Jianqing [1 ,3 ]
机构
[1] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Inst Biomed Sci, Shanghai 200433, Peoples R China
[2] Tisinghua Univ, Peking Union Med Coll, Beijing, Peoples R China
[3] Fudan Univ, Key Lab Med Mol Virol, Shanghai Med Coll, Shanghai 200433, Peoples R China
关键词
N-LINKED GLYCOSYLATION; VIRUS TYPE-1 SF162; BINDING-SITE; CORECEPTOR USAGE; V3; LOOP; GP120; GLYCAN; CD4; ESCAPE; V1/V2;
D O I
10.1089/aid.2009.0228
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The aim of this study was to test whether deglycosylation of an HIV-1 AE recombinant-derived gp140 could enhance the induction of neutralizing antibodies. N-to-Q mutations were introduced in the V1/V2 ( m157/161) or V4 (m382/388) loops by using overlapping PCR. BALB/c mice were inoculated with different DNA vaccines at weeks 0, 2, 4, and 7. The Elispot assay was used to quantify Env-specific T-cell immunity, and the TZM-bl cell-based in vitro neutralizing assay with primary isolates was used to assess humoral immune responses. Our data showed that two mutant DNA vaccines, designated m157/161 and m382/388, mounted total T-cell responses that were at levels similar those of the unmutated vaccine. Although the levels of binding antibodies elicited by the two mutants were significantly lower than the levels elicited by the unmutated vaccine, cross-reactive neutralizing antibodies were observed only in the sera that received the mutant DNA vaccines. These data demonstrate that deglycosylation of HIV-1 Env could enhance the capacity to elicit cross-reactive neutralizing antibodies.
引用
收藏
页码:569 / 575
页数:7
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