Since its discovery, HIV has posed a major threat to human health, affecting millions worldwide. Scientists have spent countless hours looking for treatments and attempting to develop vaccines. But now, scientists have found an alternative to conventional vaccines: an injection that shows promise in preventing the spread of HIV.

HIV presents a challenge to vaccines because it changes so rapidly. Studies have shown there are certain antibodies that can broadly neutralize HIV-1, preventing it from infecting cells. But these antibodies can only effectively neutralize 10 to 50 percent of HIV-1 isolates—to provide protection, you'd need unrealistically high levels of the antibodies in your system. So the search for development of an effective vaccine has continued.

Recently, scientists have designed an antibody (they're calling it eCDF-Ig) that simultaneously binds two sites on the virus' surface, neutralizing HIV more efficiently than previous antibodies.

HIV enters cells by sticking to two different proteins on their surface: CD4 and CCR5. These researchers specifically engineered their new antibody to target the two proteins on the viral envelope that mediate this binding: the CD4 receptor and a coreceptor that recognizes CCR5. The hope was that having two sites would increase targeting efficiency.

The CD4 receptor was chosen because it is highly conserved across a broad range of HIV variants. There's already an antibody called CD4-Ig that binds specifically to the CD4 receptor and has been heavily investigated in the past; these investigations revealed that targeting CD4 can neutralize most viral isolates. CD4-Ig is also harmless in humans. However, on its own, CD4-Ig has a lower affinity to the virus than other antibodies, limiting its efficacy.

So the scientists chose to target the coreceptor to CCR5 as well. The researchers designed several antibodies that were a fusion of CD4-Ig with various proteins that bind to the CCR5 coreceptor (called CCR5-mimetic proteins). They reasoned that fusion of these elements would enable an antibody to bind cooperatively, with more success than either molecule alone. They tested these antibodies on strains of HIV-1 and HIV-2 that resist known neutralizing antibodies. They found that a specific fusion antibody, eCDF-Ig, consistently blocked a wide panel of HIV-1 isolates at much lower concentrations than those required for CD4-Ig.

The researchers also performed binding studies to understand specifically why eCDF-Ig is so much more potent than other antibodies. This potency was found to be caused by a higher binding strength and a decreased negative effect on the immune system; these latter negative effects can sometimes inadvertently promote HIV infection.

Efficacy of eCD4-Ig was also assessed in more physiologically relevant conditions. When the antibody was introduced to infected human blood, it halted replication of infectious viruses at very low concentrations. Scientists then administered eCD4-Ig to mice before infecting them with HIV and found that none of the mice treated with eCD4-Ig became infected by the virus.

Finally, the team evaluated the ability to use the eCD4-Ig gene as a sort-of vaccine against HIV. They used a viral vector to deliver the gene that encodes eCD4-Ig to rhesus macaques and then challenged the animals to increasing doses of a form of HIV. Though all the control animals became infected by the HIV, none of the animals administered the experimental eCD4-Ig gene became infected. Protection from infection was seen for at least 34 weeks after inoculation in the animals.

These studies demonstrate that delivery of eCD4-Ig through viral vectors may be a promising preventative. It's not really a vaccine—the body doesn't generate antibodies of its own—but it can ensure an effective antibody is present before HIV appears.

Nature, 2014. DOI: 10.1038/nature14264 (About DOIs).