Full Length Single Chain Fc Protein (FLSC IgG1) as a Potent Antiviral Therapy Candidate: Implications for In Vivo Studies.

We have previously shown that FLSC， a chimeric protein containing HIV-1BAL gp120 and the D1 and D2 domains of human CD4， blocks the binding and entry of HIV-1 into target cells by occluding CCR5， the major HIV-1 coreceptor. In an effort to improve the antiviral potential of FLSC， we fused it with the hinge-CH2-CH3 region of human IgG1. The IgG moiety should increase both the affinity and stability in vivo of FLSC， due to the resultant bivalency and an extended serum half-life， thereby increasing its antiviral potency. We previously showed that (FLSC) IgG1 indeed had greater antiviral activity against T cell infections. Here we extend these results to macrophages， for which (FLSC) IgG1 has a more potent antiviral activity than FLSC alone， due in part to its higher binding affinity for CCR5. We also test both compounds in a relevant humanized mouse model and show that， as anticipated， the IgG1 moiety confers a greatly extended half-life. These data， taken together with previous results， suggest potential clinical utility for (FLSC) IgG1 and support further developmental work toward eventual clinical trials.