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J Immunol. 2019 Feb 1;202(3):799-804. doi: 10.4049/jimmunol.1801085. Epub 2018 Dec 28.

Human Anti-HIV-1 gp120 Monoclonal Antibodies with Neutralizing Activity Cloned from Humanized Mice Infected with HIV-1.

Author information

1
MassBiologics of the University of Massachusetts Medical School, Boston, MA 02126.
2
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655; and.
3
The Jackson Laboratory, Bar Harbor, ME 04609.
4
MassBiologics of the University of Massachusetts Medical School, Boston, MA 02126; lisa.cavacini@umassmed.edu.

Abstract

Broadly neutralizing, anti-HIV-1 gp120 mAbs have been isolated from infected individuals, and there is considerable interest in developing these reagents for Ab-based immunoprophylaxis and treatment. As a means to identify potentially new anti-HIV Abs, we exploited humanized NOD-scid IL2rγnull mice systemically infected with HIV-1 to generate a wide variety of Ag-specific human mAbs. The Abs were encoded by a diverse range of variable gene families and Ig classes, including IgA, and several showed significant levels of somatic mutation. Moreover, the isolated Abs not only bound target Ags with similar affinity as broadly neutralizing Abs, they also demonstrated neutralizing ability against multiple HIV-1 clades. The use of humanized mice will allow us to use our knowledge of HIV-1 gp120 structure and function, and the immune response targeting this protein, to generate native human prophylactic Abs to reduce the infection and spread of HIV-1.

PMID:
30593536
PMCID:
PMC6344273
DOI:
10.4049/jimmunol.1801085
[Indexed for MEDLINE]
Free PMC Article

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