Enhancing the avidity of a human recombinant anti-HIV-1 monoclonal antibody through oligomerization.
The oligomerization by chemical cross-linking of a recombinant human antiviral monoclonal antibody (MAb), r447-1, and its characterization are described. This MAb binds to an epitope residing in the hypervariable V3 region of the envelope protein (gp120/160) of HIV-1. A dimeric form of this MAb displays enhanced avidity and was found to be capable of neutralizing a greater variety of lymphoid cell culture-adapted HIV-1 variants and HIV-1 primary isolates than its monomeric form. The superior binding and breadth of reactivity of this antibody suggests it may have utility as a therapeutic and/or prophylactic agent, if it possesses an appropriate safety and immunogenicity profile.
Tsai
P K
PK
Department of Pharmaceutical Research, Merck Research Laboratories, West Point, PA 19486, USA.
Burke
C J
CJ
Irwin
J W
JW
Bruner
M W
MW
Tung
J S
JS
Hollis
G F
GF
Mark
G E
GE
Kessler
J A
JA
Boots
L J
LJ
Conley
A J
AJ
D000911:Antibodies, Monoclonal / Q000235:genetics*; D000941:Antigens / Q000276:immunology; D002845:Chromatography; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015394:Molecular Structure; D011506:Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D013997:Time Factors
D000911:Antibodies, Monoclonal; D000941:Antigens; D011506:Proteins