Immunoglobulin G-reactive antibodies from sera of healthy individuals enriched in IgG2--therapeutic potential in HIV-1 infection.
OBJECTIVE
To characterize the functional properties of natural autoantibodies capable of preventing in vitro infection by HIV-1, present in normal human serum (NHS), and denoted as IgG-reactive antibodies.


METHODS
IgG-reactive antibodies were affinity purified both from normal human serum (NHS) and from a GammaBind G Sepharose Flowthrough (GBF) fraction of NHS by affinity chromatography on IgG coupled to CNBr-activated Sepharose (IgG-Sepharose).


RESULTS
The GBF fraction was shown, by Capture ELISA relative to isotype-matched standards, to contain in addition to IgM and IgA isotypes, a low but constant level of IgG isotype. About 15% of the GBF fraction's IgG, compared to only about 0.3% of the NHS IgG, was affinity purified on IgG-Sepharose. On IgG subclass analysis, in contrast to the characteristic dominance of IgG1 in pooled NHS, the IgG-reactive antibodies obtained from NHS and from the GBF fraction each showed a dominance of IgG2. Western blot analysis confirmed the abundance of IgG2, a major IgG subclass reactive against carbohydrate antigens, and showed the presence of IgG2 dimers. The IgG-reactive antibodies separated from the GBF fraction were able to neutralize HIV-1(BaL) strain with approaching 100% and 80% effectiveness at 2 microg/ml and 0.6 microg/ml, respectively, as well as the primary isolates HIV-1(NDK) (X4-tropic isolate) and HIV-1(JR-CSF) (R5-tropic isolate) with an IC50 between 0.4 microg/ml and 1.8 microg/ml for two different preparations.


CONCLUSIONS
These findings further support our previous proposal for IgG-reactive antibody preparations to be used in the treatment of HIV-1 infected individuals.
Metlas
Radmila M
RM
Diapharm Limited, Quay House, South Esplanade, St. Peter Port, Guernsey GY1 4EJ, UK.
Srdic
Tatjana V
TV
Jenabian
Mohammad-Ali
MA
Elluru
Sriramulu
S
Carta
Laura
L
Bowker
Timothy J
TJ
Kaveri
Srini V
SV
Concas
Daniela
D
D019380:Anti-HIV Agents / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D002846:Chromatography, Affinity; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000276:immunology / Q000302:isolation & purification; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D007167:Immunotherapy / Q000379:methods; D020128:Inhibitory Concentration 50; D009500:Neutralization Tests
D019380:Anti-HIV Agents; D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G