Confronting the hypervariability of an immunodominant epitope eliciting virus neutralizing antibodies from the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1)--II. Synthetic peptides linked to HIV-1 carrier proteins gag and nef.
Confronting the hypervariability of an immunodominant epitope eliciting virus neutralizing antibodies from the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1)--II. Synthetic peptides linked to HIV-1 carrier proteins gag and nef.
复制标题
面对免疫显性表位的高度变异性，从人类免疫缺陷病毒 1 型 (HIV-1)-II 的包膜糖蛋白中引发病毒中和抗体。
DOI：
10.1016/0161-5890(91)90182-j
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发表时间：
1991
影响因子：
3.6
通讯作者：
Jiang,S
中科院分区：
文献类型：
--
作者：
Neurath,AR;Strick,N;Kolbe,H;Kieny,MP;Girard,M;Jiang,S
Combining of subtype specific peptides from the hypervariable loop of the envelope glycoprotein gp120 of divergent HIV-1 isolates may help in designing a broadly protective immunogen against HIV-1 infection. To enhance the immunogenicity of such a polyvalent antigen, in the absence of oil-containing adjuvants, it is necessary to link the peptides to a protein carrier. It is preferable to use as carriers those proteins from HIV-1 itself which may contribute to eliciting protective immunity. The structural and non-structural proteins,gagP18 andnef, respectively, which can be prepared in high yields by recombinant DNA techniques inEscherichia coli, were selected for this purpose. The corresponding peptide-protein conjugates, each containing 21 distinct peptides, were prepared using the cross-linking reagentsN-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP) orm-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sulfo-MBS). Conjugates prepared by the second method elicited ≈ 10–100 times higher levels of antibodies recognizing the homologous peptides and the HIV-1 envelope glycoproteins. The sulfo-MBS conjugation procedure preserved the antigenicity of bothgagP18 andnefand the respective conjugates elicited an immune response to these proteins. Despite the low immunization dose of single peptides (10μg) present in the mixture of peptides collectively linked to the carriers, antibody responses to most of the individual peptides were high (dilution endpoints 1: > 16,000, l: > 80,000 for thenefandgagP18 conjugates, respectively). Conjugates consisting of a multitude of HIV-1 envelope-derived peptides in combination withgagP18 andnefcarriers are expected to elicit broadly protective immunity against distinct HIV-1 subtypes.
