| 1. |
- Abayneh, Sisay A, et al.
(författare)
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Sensitivity of HIV-1 primary isolates to human anti-CD40 antibody-mediated suppression is related to co-receptor use
- 2008
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 24:3, s. 447-452
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Tidskriftsartikel (refereegranskat)abstract
- The effect of CD40 ligation on infection by HIV-1 primary isolates with different R5 phenotypes was evaluated with a novel set of anti-CD40 monoclonal antibodies originating from a human phage display library. Five human monoclonal anti-CD40 antibodies of IgG1 subtype characterized by the ability to activate B cells via CD40 were tested for induction of the CC-chemokines RANTES and MIP-1alpha and inhibition of HIV-1 replication in primary monocyte-derived macrophages (MDM). All activating anti-CD40 antibodies were able to induce CC-chemokines in MDM. We chose the most potent antibody, clone B44, for further experiments. This antibody had a suppressive effect on HIV-1 isolates of the R5 phenotype with limited use of CCR5/CXCR4 chimeric receptors. In comparison, HIV-1 isolates with broader use of CCR5/CXCR4 chimeric receptors or with CXCR4 use were less sensitive to anti-CD40-induced suppression. The results indicate that HIV-1 replication is inhibited by human anti-CD40 monoclonal antibodies through the mechanism of CC-chemokine induction. This effect is thus restricted to HIV-1 isolates sensitive to inhibition by CC-chemokines.
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| 2. |
- Ellmark, Peter, et al.
(författare)
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Identification of a strongly activating human anti-CD40 antibody that suppresses HIV-1 infection
- 2008
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Ingår i: AIDS Research and Human Retroviruses. - : Mary Ann Liebert Inc. - 1931-8405 .- 0889-2229. ; 24:3, s. 367-373
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Tidskriftsartikel (refereegranskat)abstract
- We characterized the functional properties of a novel set of human anti-CD40 monoclonal antibodies originating from a human phage display library and identified an antibody that strongly activates cells via the CD40 receptor for potential use in HIV therapy. The anti-CD40 antibodies were converted from a single chain antibody fragment format (scFv) to an IgG format and produced in HEK293 cells, and the binding characteristics were evaluated. Next, their ability to (1) rescue a human B cell line from induced apoptosis, (2) stimulate B cell proliferation, and (3) block the CD40-CD40L interaction was determined. Finally, the most activating anti-CD40 antibody was tested for its ability to block HIV-1 infection in a monocyte-derived cell line.The different anti-CD40 antibodies, A24, B44, E30, F33, and A2-54, displayed a wide variety of binding and functional properties. In particular, B44 showed a very strong ability to activate normal human B cells and, in addition, did not block the CD40-CD40L interaction. This antibody was able to suppress HIV-1 infection in a human cell line (MonoMac 1) and may be a potential therapeutic candidate in HIV infection.
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