Scientists from the National Institute of Allergy and Infectious Diseases (NIAID) and Sanofi reported in Science yesterday that they engineered a three-pronged antibody against SHIV that performs better than individual natural antibodies.
The three-pronged antibody also stopped a greater number of HIV strains from infecting cells in the laboratory more potently than natural, single antibodies. It does this by binding to three different critical sites on HIV and was based on three individual HIV antibodies. The researchers tested dozens of bispecific and trispecific antibodies to find the best-performing combination. The most successful combination combined the structures of three HIV antibodies called VRC01, PGDM1400, and 10E8v4.
"Combinations of antibodies that each bind to a distinct site on HIV may best overcome the defenses of the virus in the effort to achieve effective antibody-based treatment and prevention," said Anthony S. Fauci, M.D., director of the NIAID, part of NIH. "The concept of having a single antibody that binds to three unique sites on HIV is certainly an intriguing approach for investigators to pursue."
NIAID scientists tested this trispecific antibody in an experiment involving monkeys and two strains of SHIV. One SHIV strain is sensitive to neutralization by VRC01 and the trispecific antibody but resistant to neutralization by PGDM1400. The other SHIV strain is sensitive to neutralization by PGDM1400 and the trispecific antibody but resistant to neutralization by VRC01.
The NIAID researchers gave infusions of VRC01 to one-third of the monkeys, PGDM1400 to another third, and the trispecific antibody to the last third of monkeys. Five days later, the researchers exposed all the monkeys to both SHIV strains. The only group of monkeys that did not become infected was the ones that received the trispecific antibody.
Plans are now underway with the hopes of conducting a Phase 1 trial. The study authors believe that this prototype is not only useful for those infected with HIV, but other diseases as well.
Image: A diagram of the 'three-in-one' HIV antibody. The blue, purple and green segments each bind to a different critical site on the virus. Image courtesy of the NIAID.