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Hum Gene Ther. 2015 Sep;26(9):622-34. doi: 10.1089/hum.2014.146. Epub 2015 Aug 11.

Adenovirus-Vectored Broadly Neutralizing Antibodies Directed Against gp120 Prevent Human Immunodeficiency Virus Type 1 Acquisition in Humanized Mice.

Author information

1
Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine , New Haven, Connecticut.

Abstract

Despite nearly three decades of research, a safe and effective vaccine against human immunodeficiency virus type 1 (HIV-1) has yet to be achieved. More recently, the discovery of highly potent anti-gp160 broadly neutralizing antibodies (bNAbs) has garnered renewed interest in using antibody-based prophylactic and therapeutic approaches. Here, we encoded bNAbs in first-generation adenoviral (ADV) vectors, which have the distinctive features of a large coding capacity and ease of propagation. A single intramuscular injection of ADV-vectorized bNAbs in humanized mice generated high serum levels of bNAbs that provided protection against multiple repeated challenges with a high dose of HIV-1, prevented depletion of peripheral CD4(+) T cells, and reduced plasma viral loads to below detection limits. Our results suggest that ADV vectors may be a viable option for the prophylactic and perhaps therapeutic use of bNAbs in humans.

PMID:
25953321
PMCID:
PMC4575530
DOI:
10.1089/hum.2014.146
[Indexed for MEDLINE]
Free PMC Article

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