期刊
VACCINE
卷 23, 期 13, 页码 1559-1573出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2004.09.037
关键词
antibody engineering; immunotargeting; HIV-1; gp4l
2F5 is one of the few broadly neutralizing monoclonal antibodies against type I Human Immunodeficiency Virus (HIV-1). It recognizes the amino acid sequence ELDKWAS in gp41. We have previously identified a number of immunotargeting 2F5-reactive candidate immunogens. Three of them (designated H-BT1-3) have the ELDKWAS sequence constrained at P-turn sites within the immunoglobulin heavy chain. Two others (L-CT and L-CTx3) have the sequence attached at the C-terminus of the immunoglobulin light chain with minimal conformational constraints. In the present investigation, the H-BTs were found to bind 2F5 with up to 10-fold higher affinities than their unconstrained counterpart. When used as immunogens, immunogen-specific antibodies were induced with or without adjuvant, confirming the immunotargeting potential of these immunogen constructs. While HIV-1 gp 160 cross-reactive antibodies were induced, virus neutralization was not detected. Thus, factors other than 2175 binding affinity may have a critical role to play in the design of a 2F5-based vaccine. (c) 2004 Elsevier Ltd. All rights reserved.
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