Our Solution

The immune system responds to viral or bacterial pathogens by generating antibodies. Antibodies can provide immunity against viral infections by sticking to viruses, thereby physically blocking infection of host cells. However, HIV evolves to escape antibody responses faster than the immune system can generate new antibodies that recognize the escaped viruses. The inability of the immune system to keep pace with viral escape has two important consequences for treating and preventing HIV infection: Individual patients are rarely able to generate an effective antibody response that suppresses virus replication. On the population level, continuous cycles of viral escape since the beginning of the HIV pandemic has generated extraordinary viral diversity. This diversity presents a significant obstacle to vaccine development.

As an alternative to conventional vaccine approaches for HIV, we engineered a synthetic antibody from the receptors that HIV uses to infect T cells.

HIV recognizes two proteins, CD4 and CCR5, which are displayed on the surfaces of its susceptible host cells. In order to construct an antibody that is effective against all strains of HIV, and that presents intrinsic barriers to viral escape, we fused the parts of CD4 and CCR5 that HIV recognizes onto an antibody. We named the resulting synthetic antibody “eCD4-Ig.” eCD4-Ig can be injected directly as a therapeutic drug. Alternatively, eCD4-Ig can be delivered as DNA that is introduced into muscle cells by a single injection with a viral vector. Using this strategy in monkeys, we sustained protective concentrations of eCD4-Ig in blood for the long-term. This approach provided durable protection against infection of monkeys with large, intravenous doses of live virus, and also may be effective as a therapy for treating an ongoing infection.