Unknown

Dataset Information

0

Antibody conjugation approach enhances breadth and potency of neutralization of anti-HIV-1 antibodies and CD4-IgG.


ABSTRACT: Broadly neutralizing antibodies PG9 and PG16 effectively neutralize 70 to 80% of circulating HIV-1 isolates. In this study, the neutralization abilities of PG9 and PG16 were further enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. A novel air-stable diazonium hexafluorophosphate reagent that allows for rapid, tyrosine-selective functionalization of proteins and antibodies under mild conditions was used to prepare a series of aplaviroc-conjugated antibodies, including b12, 2G12, PG9, PG16, and CD4-IgG. The conjugated antibodies blocked HIV-1 entry through two mechanisms: by binding to the virus itself and by blocking the CCR5 receptor on host cells. Chemical modification did not significantly alter the potency of the parent antibodies against nonresistant HIV-1 strains. Conjugation did not alter the pharmacokinetics of a model IgG in blood. The PG9-aplaviroc conjugate was tested against a panel of 117 HIV-1 strains and was found to neutralize 100% of the viruses. PG9-aplaviroc conjugate IC50s were lower than those of PG9 in neutralization studies of 36 of the 117 HIV-1 strains. These results support this new approach to bispecific antibodies and offer a potential new strategy for combining HIV-1 therapies.

SUBMITTER: Gavrilyuk J 

PROVIDER: S-EPMC3624287 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Antibody conjugation approach enhances breadth and potency of neutralization of anti-HIV-1 antibodies and CD4-IgG.

Gavrilyuk Julia J   Ban Hitoshi H   Uehara Hisatoshi H   Sirk Shannon J SJ   Saye-Francisco Karen K   Cuevas Angelica A   Zablowsky Elise E   Oza Avinash A   Seaman Michael S MS   Burton Dennis R DR   Barbas Carlos F CF  

Journal of virology 20130220 9


Broadly neutralizing antibodies PG9 and PG16 effectively neutralize 70 to 80% of circulating HIV-1 isolates. In this study, the neutralization abilities of PG9 and PG16 were further enhanced by bioconjugation with aplaviroc, a small-molecule inhibitor of virus entry into host cells. A novel air-stable diazonium hexafluorophosphate reagent that allows for rapid, tyrosine-selective functionalization of proteins and antibodies under mild conditions was used to prepare a series of aplaviroc-conjugat  ...[more]

Similar Datasets

| S-EPMC4325730 | biostudies-literature
| S-EPMC4970321 | biostudies-literature
| S-EPMC10528384 | biostudies-literature
| S-EPMC3243554 | biostudies-literature
| S-EPMC4810720 | biostudies-literature
| S-EPMC5770152 | biostudies-literature
| S-EPMC6300260 | biostudies-literature
| S-EPMC4497764 | biostudies-literature
| S-EPMC6260891 | biostudies-other
| S-EPMC4465343 | biostudies-literature