Neutralization of HIV-1 by F105, a human monoclonal antibody to the CD4 binding site of gp120.
The functional ability of the human monoclonal antibody (HMab) F105 to neutralize commonly available laboratory strains and a selection of primary isolates of human immunodeficiency virus (HIV)-1 was studied. F105 is representative of a class of human antibodies that react with conformational epitopes within the discontinuous CD4 binding site on HIV-1 envelope glycoprotein gp120. F105 binds with relatively similar affinities to native antigen expressed on the surfaces of cells infected with each of five laboratory isolates tested (IIIB, SF2, MN, RF, and CC) and neutralizes SF2, IIIB, and MN with concentrations of antibody ranging from 140 ng to 10 micrograms/ml. Nonetheless, neutralization by F105 alone of RF and CC is poor at modest antibody concentrations despite high affinity binding to surface gp120 on infected cells. Neutralization of HIV-1 strains by F105 is unaffected by normal sera and cooperativity is observed with serum samples from HIV-1 infected patients. Of significance, neutralization of RF and MN by F105 is enhanced by some HIV-seropositive sera at low concentrations. F105 also neutralized 30% of HIV-1 primary isolates in lymphocyte cultures. Although it is unclear how relevant in vitro studies will be to in vivo events, these data allow comparison of F105 with other HMabs to the CD4 binding site and V3 loop and provide an in vitro reference for in vivo activity. These studies demonstrate that antibody interactions among different classes of antibodies may be important in in vivo neutralization of HIV-1.
Posner
M R
MR
Division of Hematology/Oncology, New England Deaconess Hospital, Boston, MA 02215.
Cavacini
L A
LA
Emes
C L
CL
Power
J
J
Byrn
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D002460:Cell Line; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests / Q000379:methods*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120