Single Engineered Antibody Binds to 3 Unique Sites on HIV, Potential Treatment Option

A 3-pronged antibody could help treat and prevent HIV in the future.

In a study published in Science, investigators engineered trispecific antibodies to allow a single molecule to interact with 3 independent HIV-1 envelope determinants: the CD4 binding site, the membrane proximal external region, and the V1V2 glycan site.

To test the trispecific antibody, the investigators used monkeys and 2 strains of SHIV, according to a release from the National Institutes of Health (NIH).

One strain was found to be sensitive to neutralization by VRC01 and the trispecific antibody, but resistant to neutralization by PGDM1400. Whereas the other SHIV strain is sensitive to neutralization by PGDM1400 and the trispecific antibody, but resistant to neutralization by VRC01.

Eight of the monkeys received infusions of VRC01, another 8 monkeys received PGDM1400, and the third group of 8 monkeys received the trispecific antibody. After 5 days, all 24 monkeys were exposed to both strains of SHIV.

The results of the study showed 5 of 8 monkeys in the PGDM1400 arm and 6 of 8 in the VRC01 arm became infected with SHIV; however, none of the monkeys in the trispecific antibody arm became infected.

“Trispecific antibodies exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to human bnAbs, and conferred complete immunity against a mixture of SHIVs in non-human primates in contrast to single bnAbs,” the authors wrote.

Plans to test the trispecific antibodies in human clinical trials are already underway, according to the release.

Sanofi is manufacturing the trispecific antibody for use in a phase 1 trial to test the antibody’s safety and pharmacokinetics in healthy individuals beginning in late 2018. Discussions are also taking place regarding a separate phase 1 clinical trial of the antibody in individuals with HIV.

“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,” Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in the release. “The concept of having a single antibody that binds to 3 unique sites on HIV is certainly an intriguing approach for investigators to pursue.”