Neutralizing anti-HIV antibodies develop in a humanized
Name
Seung-2012-Neutralizing anti-HI.pdf
Size
165.21 KB
Format
Adobe PDF
Checksum (MD5)
2bf073cc6d441be783b2ef9d47f5199b
Author(s)
Seung, E.
Dugast, Anne-Sophie
Dudek, T.
Mattoo, H.
Vrbanac, V.
Tivey, T.
Murooka, T.
Cariappa, A.
Luster, Andrew D.
Pillai, S.
Date Issued
September 2012
Journal
Retrovirology
Publisher
BioMed Central Ltd.
Citation
Seung, E et al. “Neutralizing anti-HIV Antibodies Develop in a Humanized Mouse Model of HIV-1 Infection.” Retrovirology 9.Suppl 2 (2012): P60. Web.
Version
Final published version
Abstract
Background:
In BLT (bone marrow-liver-thymus) humanized mice, human thymocytes are educated by autologous human thymic tissue, resulting in functional human T cells capable of rapidly selecting for CTL escape mutations in HIV. In contrast, limitations to B cell maturation have been noted. But despite this, we show for the first time that HIV infected BLT mice can produce class-switched anti-HIV antibodies with neutralizing activities.
Methods:
Humanized BLT mice were generated by transplanting irradiated NOD-scid/IL2rgnull (NSG) mice with fetal thymus and liver fragments and then injecting them with autologous human CD34+ stem cells. BLT mice were then infected with HIVJRCSF and bled at various time-points. HIV neutralizing activity was measured using Tat-induced luciferase reporter TZM-bl cells.
Results:
Human transitional B cells were present in greater frequencies in BLT mice than adult humans. Most of these cells had a T1 phenotype in the blood and spleen. But despite this B cell maturation defect, class-switched IgG Abs against various HIV proteins were detected by Western Blot in HIV-infected BLT mice. Using ELISA to determine anti-p24 IgG Ab titers, Abs were present as early as 8 weeks post infection (p.i.), with peak Ab titers seen after 15 weeks. One infected mouse demonstrated a peak titer similar to that seen in a chronically infected human. Finally, plasma samples from infected BLT mice after 22 weeks p.i. demonstrated neutralizing activities against the challenge virus. Average IC50 neutralizing titers in these mice were similar to those from infected human samples.
Conclusion:
The ability of humanized BLT mice to generate functional humoral immune responses may be further improved by strategies to improve their B cell maturation, which will further improve the potential of these mice to become a model system to study candidate HIV vaccines and therapies.
Description
From AIDS Vaccine 2012, Boston, MA, USA. 9-12 September 2012.
MIT Department
Ragon Institute of MGH, MIT and Harvard
Terms of Use
Creative Commons Attribution
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1186/1742-4690-9-s2-p60
