Sensitivity of HIV-1 primary isolates to human anti-CD40 antibody-mediated suppression is related to co-receptor use

• 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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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

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