Antibodies to a superantigenic glycoprotein 120 epitope as the basis for developing an HIV vaccine.
Antibodies to a superantigenic glycoprotein 120 epitope as the basis for developing an HIV vaccine.
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DOI：
10.4049/jimmunol.1200981
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Paul S
中科院分区：
文献类型：
--
作者：
Planque SA;Mitsuda Y;Nishiyama Y;Karle S;Boivin S;Salas M;Morris MK;Hara M;Liao G;Massey RJ;Hanson CV;Paul S
Failure to induce synthesis of neutralizing antibodies to the CD4 binding determinant (CD4BD) of gp120, a central objective in HIV vaccine research, has been alternately ascribed to insufficient immunogen binding to antibodies in their germline variable (V) region configuration expressed as B cell receptors, insufficient adaptive mutations in antibody variable (V) regions and conformational instability of gp120. We employed peptide analogs of gp120 residues 421-433 (CD4BDcore) to identify antibodies produced without prior exposure to HIV (constitutive antibodies). The CD4BDcore peptide was recognized by single chain Fv (scFv) fragments from non-infected humans with lupus that neutralized genetically diverse strains belonging to various HIV subtypes. Replacing the framework (FR) segments of a VH4-family scFv with the corresponding VH3-family FRs from scFv JL427 improved the CD4BDcore peptide binding activity, suggesting a CD4BDcore binding site outside the pocket formed by the complementarity determining regions. Replacement mutations in the FR site vicinity suggested the potential for adaptive improvement. A very small subset of serum CD4BDcore-specific serum IgAs from non-infected humans without autoimmune disease isolated by epitope-specific chromatography neutralized the virus potently. A CD4BDcore-specific, HIV neutralizing murine IgM with heavy and light chain V regions (VH and VL regions) free of immunogen-driven somatic mutations was induced by immunization with a CD4BDcore peptide analog containing an electrophilic group that binds B cells covalently. The studies indicate broad and potent HIV neutralization by constitutive antibodies as an innate, germline-encoded activity directed to the superantigenic CD4BDcore epitope that is available for amplification for vaccination against HIV.
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影响因子：
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