Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro.

Abstract:

:A panel of 20 recombinant Fab fragments reactive with the surface glycoprotein gp120 of human type 1 immunodeficiency virus (HIV-1) were examined for their ability to neutralize MN and IIIB strains of the virus. Neutralization was determined as the ability of the Fab fragments to inhibit infection as measured in both a p24 ELISA and a syncytium-formation assay. One group of closely sequence-related Fab fragments was found to neutralize virus in both assays with a 50% neutralization titer at approximately 1 micrograms/ml. Another Fab neutralized in the p24 ELISA but not in the syncytium assay. The other Fab fragments showed weak or no neutralizing ability. The results imply that virion aggregation or crosslinking of gp120 molecules on the virion surface is not an absolute requirement for HIV-1 neutralization. Further, all of the Fab fragments were shown to be competitive with soluble CD4 for binding to gp120 and yet few neutralized the virus effectively, implying that the mechanism of neutralization in this case may not involve receptor blocking. The observation of a preponderance of high-affinity Fab fragments with poor or no neutralizing ability could have implications for vaccine strategies.

authors

Barbas CF 3rd,Björling E,Chiodi F,Dunlop N,Cababa D,Jones TM,Zebedee SL,Persson MA,Nara PL,Norrby E

doi

10.1073/pnas.89.19.9339

keywords:

subject

Has Abstract,Author List Incomplete

pub_date

1992-10-01 00:00:00

pages

9339-43

issue

19

eissn

0027-8424

issn

1091-6490

journal_volume

89

pub_type

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