A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier

Alicia McFarren, Lillie Lopez, Dionna W. Williams, Mike Veenstra, Ruth A. Bryan, Aliza Goldsmith, Alfred Morgenstern, Frank Bruchertseifer, Susan Zolla-Pazner, Miroslaw K. Gorny, Eliseo Eugenin, Joan W. Berman, Ekaterina Dadachova

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Objective: Many HIV patients on combined antiretroviral therapy exhibit HIV-associated neurocognitive disorders because the brain becomes a viral reservoir. There is a need for therapeutics that can enter the central nervous system (CNS) and eradicate the virus. Design: Radiolabeled human mAb 2556 to HIV gp41 selectively kills HIV-infected cells in vivo and in vitro. Here we tested the ability of 213Bi-2556 to cross a tissue culture model of the human blood brain barrier and kill HIV-infected peripheral blood mononuclear cells (PBMCs) and monocytes on the CNS side of the barrier. Methods: 2556 mAb isoelectric point was determined with isoelectric focusing. The ability of radiolabeled 2556 to penetrate through the barrier was studied by adding it to the upper chamber of the barriers and its penetration into the CNS side was followed for 5 h. To assess the ability of 213 Bi-2556 to kill the HIV-infected cells on the CNS side of barrier, the HIV-infected and uninfected PBMCs and monocytes were allowed to transmigrate across the barriers overnight followed by application of 213 Bi-2556 or control mAb 213 Bi-1418 to the top of the barrier. Killing of cells was measured by TUNEL and Trypan blue assays. The barriers were examined by confocal microscopy for overt damage. Results: The isoelectric point of 213 Bi-2556 was 9.6 enabling its penetration through the barrier by transcytosis. 213 Bi-2556 killed significantly more transmigrated HIV-infected cells in comparison to 213 Bi-1418 and uninfected cells. No overt damage to barriers was observed. Conclusion: We demonstrated that 213 Bi-2556 mAb crossed an in-vitro human blood brain barrier and specifically killed transmigrated HIV-infected PBMCs and monocytes without overt damage to the barrier.

Original languageEnglish (US)
Pages (from-to)563-571
Number of pages9
JournalAIDS
Volume30
Issue number4
DOIs
StatePublished - Feb 20 2016
Externally publishedYes

Fingerprint

Blood-Brain Barrier
HIV
Antibodies
Aptitude
Central Nervous System
Monocytes
Blood Cells
Isoelectric Point
HIV Envelope Protein gp41
Transcytosis
Trypan Blue
In Situ Nick-End Labeling
Isoelectric Focusing
Confocal Microscopy
Viruses
Brain
Therapeutics

Keywords

  • 213-Bismuth
  • HAND
  • HIV-infected human peripheral blood mononuclear cells
  • in-vitro human blood brain barrier model
  • monocytes
  • neuroaids
  • radioimmunotherapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

McFarren, A., Lopez, L., Williams, D. W., Veenstra, M., Bryan, R. A., Goldsmith, A., ... Dadachova, E. (2016). A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. AIDS, 30(4), 563-571. https://doi.org/10.1097/QAD.0000000000000968

A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. / McFarren, Alicia; Lopez, Lillie; Williams, Dionna W.; Veenstra, Mike; Bryan, Ruth A.; Goldsmith, Aliza; Morgenstern, Alfred; Bruchertseifer, Frank; Zolla-Pazner, Susan; Gorny, Miroslaw K.; Eugenin, Eliseo; Berman, Joan W.; Dadachova, Ekaterina.

In: AIDS, Vol. 30, No. 4, 20.02.2016, p. 563-571.

Research output: Contribution to journalArticle

McFarren, A, Lopez, L, Williams, DW, Veenstra, M, Bryan, RA, Goldsmith, A, Morgenstern, A, Bruchertseifer, F, Zolla-Pazner, S, Gorny, MK, Eugenin, E, Berman, JW & Dadachova, E 2016, 'A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier', AIDS, vol. 30, no. 4, pp. 563-571. https://doi.org/10.1097/QAD.0000000000000968
McFarren, Alicia ; Lopez, Lillie ; Williams, Dionna W. ; Veenstra, Mike ; Bryan, Ruth A. ; Goldsmith, Aliza ; Morgenstern, Alfred ; Bruchertseifer, Frank ; Zolla-Pazner, Susan ; Gorny, Miroslaw K. ; Eugenin, Eliseo ; Berman, Joan W. ; Dadachova, Ekaterina. / A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. In: AIDS. 2016 ; Vol. 30, No. 4. pp. 563-571.
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abstract = "Objective: Many HIV patients on combined antiretroviral therapy exhibit HIV-associated neurocognitive disorders because the brain becomes a viral reservoir. There is a need for therapeutics that can enter the central nervous system (CNS) and eradicate the virus. Design: Radiolabeled human mAb 2556 to HIV gp41 selectively kills HIV-infected cells in vivo and in vitro. Here we tested the ability of 213Bi-2556 to cross a tissue culture model of the human blood brain barrier and kill HIV-infected peripheral blood mononuclear cells (PBMCs) and monocytes on the CNS side of the barrier. Methods: 2556 mAb isoelectric point was determined with isoelectric focusing. The ability of radiolabeled 2556 to penetrate through the barrier was studied by adding it to the upper chamber of the barriers and its penetration into the CNS side was followed for 5 h. To assess the ability of 213 Bi-2556 to kill the HIV-infected cells on the CNS side of barrier, the HIV-infected and uninfected PBMCs and monocytes were allowed to transmigrate across the barriers overnight followed by application of 213 Bi-2556 or control mAb 213 Bi-1418 to the top of the barrier. Killing of cells was measured by TUNEL and Trypan blue assays. The barriers were examined by confocal microscopy for overt damage. Results: The isoelectric point of 213 Bi-2556 was 9.6 enabling its penetration through the barrier by transcytosis. 213 Bi-2556 killed significantly more transmigrated HIV-infected cells in comparison to 213 Bi-1418 and uninfected cells. No overt damage to barriers was observed. Conclusion: We demonstrated that 213 Bi-2556 mAb crossed an in-vitro human blood brain barrier and specifically killed transmigrated HIV-infected PBMCs and monocytes without overt damage to the barrier.",
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AU - McFarren, Alicia

AU - Lopez, Lillie

AU - Williams, Dionna W.

AU - Veenstra, Mike

AU - Bryan, Ruth A.

AU - Goldsmith, Aliza

AU - Morgenstern, Alfred

AU - Bruchertseifer, Frank

AU - Zolla-Pazner, Susan

AU - Gorny, Miroslaw K.

AU - Eugenin, Eliseo

AU - Berman, Joan W.

AU - Dadachova, Ekaterina

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