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“Cautious optimism” for three-pronged antibody that blocks simian HIV

, by Warren Tong

A recent study published in Science described the success of a newly engineered “three-pronged” broadly neutralizing antibody (bnAb) in preventing simian HIV (SHIV) infection in monkeys. This is the first study to demonstrate the efficacy of a bnAb that targets three different sites on the virus—a characteristic that provides protection against more diverse strains of HIV than previously studied bnAbs.


Diagram of the three-pronged antibody. The blue, purple and green segments each bind to a different critical site on HIV; photo: SANOFI

Antibodies are infection-fighting proteins produced by the body’s immune system to help destroy foreign substances like viruses. Antibodies “neutralize” viruses by binding to receptors on the surface of viruses, which then prevent the virus from doing any harm. Usually, antibodies can neutralize only one strain of a virus. Broadly neutralizing antibodies, as their name implies, can identify and neutralize different strains of a virus, although HIV can still evade bnAbs as the virus mutates.

“Broadly neutralizing antibodies have been attractive for their potential to target a wide range of HIV strains, yet have been limited in their experimental utility by the rapid evolution of the virus and subsequent emergence of viruses that escape immune control,” Benjamin Young, MD, PhD, senior vice president and chief medical officer of the International Association of Providers in AIDS Care (IAPAC) told BETA.

“One intriguing strategy to deal with this was shown in [the current study]—making a bnAb with three different targets in one. The authors showed this strategy worked in protecting monkeys against infection with a mixture of different SHIV strains, suggesting that the strategy might be of benefit in humans. We won’t know tomorrow, or in the near future, if multivalent bnAbs will lead to successful preventive vaccines, yet we should view this report with cautious optimism,” said Young.

Effectiveness of the three-pronged antibody

Ling Xu and colleagues combined the structures from three HIV bnAbs (VRC01, PGDM1400 and 10E8v4) into one three-pronged antibody. They then compared the three-pronged antibody’s ability to block HIV to the effectiveness of VRC01 and PGDM1400 alone.

In the study, eight monkeys were given infusions of VRC01, another eight monkeys were given infusions of PGDM1400, and another eight monkeys were given infusions of the three-pronged antibody. Five days later, the monkeys were exposed to two different strains of SHIV.

Overall, five of the eight (62%) monkeys treated with PGDM1400 became infected and six of the eight (75%) monkeys treated with VRC01 became infected. There were zero infections among the eight monkeys treated with the three-pronged antibody.

“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, MD, director of the National Institute of Allergy and Infectious Diseases (NIAID).

“The concept of having a single antibody that binds to three unique sites on HIV is certainly an intriguing approach for investigators to pursue,” Fauci said.

Could the three-pronged antibody be used in HIV treatment?

In addition to HIV prevention, the three-pronged antibody also may hold potential for HIV treatment.

Previous research has found that infusions with a single bnAb can reduce viral loads in people living with HIV, and delay viral rebound when people stop treatment. Future research may examine if the three-pronged antibody can be used to treat HIV or help prolong viral control in the absence of antiretroviral therapy.

There are limitations to this early study, said Young, which limit the conclusions that can be drawn about the three-pronged antibody at this stage.

“The study wasn’t in humans, nor directed against HIV. It’s also possible that while thoughtfully selected, the mixture of SHIV doesn’t represent relevant possible HIV genetic variants. And perhaps most important, the study can’t address the safety of the bnAb in humans,” said Young.

The researchers plan to move on to early-phase studies in humans to test the three-pronged antibody as both long-acting HIV prevention and treatment. The NIH will first conduct a phase 1 study to test the three-pronged antibody’s safety and pharmacokinetics (how the body absorbs and reacts to the drug) in humans starting in late 2018.


Warren Tong is a freelance health and science journalist, with an extensive background writing about HIV and hepatitis C.


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