PMID- 11803079
OWN - NLM
STAT- MEDLINE
DCOM- 20020529
LR  - 20190728
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 20
IP  - 7-8
DP  - 2002 Jan 15
TI  - Construction of recombinant targeting immunogens incorporating an HIV-1 
      neutralizing epitope into sites of differing conformational constraint.
PG  - 1169-80
AB  - 2F5 is one of the very few monoclonal antibodies with the capacity to neutralize 
      a wide spectrum of type 1 human immunodeficiency virus (HIV-1) strains and 
      primary isolates. Constructing an immunogen that contains a conformational mimic 
      of the epitope recognized by 2F5 could provide the means to induce a broadly 
      neutralizing anti-HIV-1 antibody response. Thus, in an effort to create a 
      targeted, adjuvant-independent immunogen able to induce a 2F5-like antibody 
      response, the gp41 sequence recognized by 2F5 (ELDKWAS) was genetically 
      incorporated into different regions of an antibody specific for a framework 
      determinant on human leukocyte antigen (HLA)-DR. All constructs were expressed, 
      secreted from Sf9 insect cells, and found to retain the anti-HLA-DR specificity 
      of the parental antibody. Three of the four constructs in which the ELDKWAS 
      sequence was incorporated into a beta-turn (BT)-like conformational site were 
      recognized by the 2F5 antibody. In contrast, none of the five constructs with the 
      same sequence incorporated into surface-exposed regions of helical turn had any 
      detectable 2F5 reactivity. In addition to demonstrating the significant 
      plasticity of several regions in the antibody molecule in terms of accepting 
      foreign sequences without loss of expression or binding specificity, these 
      results also suggest that the native epitope recognized by the 2F5 antibody may 
      be more beta-turn-like than helical in conformation. Importantly, with respect to 
      vaccine development, the 2F5-reactive antibody constructs represent candidate 
      immunogens for the adjuvant-independent induction of an HIV-1, neutralizing 
      2F5-like antibody response in humans.
FAU - Ho, Jason
AU  - Ho J
AD  - Department of Immunology, Medical Sciences Building, 1 Kings College Circle, 
      University of Toronto, Ont., M5S 1A8, Toronto, Canada.
FAU - MacDonald, Kelly S
AU  - MacDonald KS
FAU - Barber, Brian H
AU  - Barber BH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Epitopes)
RN  - 0 (HIV Antibodies)
RN  - 0 (HIV Envelope Protein gp41)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Antibodies, Monoclonal/*immunology
MH  - Base Sequence
MH  - Epitopes
MH  - HIV Antibodies/chemistry/*genetics/immunology
MH  - HIV Envelope Protein gp41/chemistry/*immunology
MH  - HIV-1/*immunology
MH  - HLA-DR Antigens/metabolism
MH  - Histocompatibility Antigens Class II/immunology
MH  - Humans
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Protein Conformation
MH  - *Protein Engineering
MH  - Recombinant Proteins/immunology
EDAT- 2002/01/23 10:00
MHDA- 2002/05/30 10:01
CRDT- 2002/01/23 10:00
PHST- 2002/01/23 10:00 [pubmed]
PHST- 2002/05/30 10:01 [medline]
PHST- 2002/01/23 10:00 [entrez]
AID - S0264410X01004418 [pii]
AID - 10.1016/s0264-410x(01)00441-8 [doi]
PST - ppublish
SO  - Vaccine. 2002 Jan 15;20(7-8):1169-80. doi: 10.1016/s0264-410x(01)00441-8.