HIV Breakthrough : An Antibody that Attacks 99% of HIV Strains
The development of an effective AIDS vaccine has been challenging due to viral genetic diversity and the difficulty in generating broadly neutralizing antibodies (bnAbs). But now, scientists from Sanofi and the NIH have collaborated to develop a three-pronged antibody that has shown promise in a primate model for HIV.
The laboratory-made three in one antibody has been found to protect monkeys from infection with two strains of SHIV, a monkey form of HIV, better than individual natural antibodies from which the engineered antibody is derived. Natural antibodies recognize a single target on a foreign protein. In this study, antibodies were engineered to recognize three different target sites in one molecule. These HIV “trispecific” antibodies were highly effective in suppressing virus growth and infection.
“Unlike natural antibodies, trispecific antibodies engage multiple targets in a single product. This approach to multi-targeting provides an opportunity to improve protection against HIV and represents a foundation for potential new treatments of cancer, immune, and infectious diseases,” said Gary Nabel, Chief Scientific Officer and Senior Vice President of Sanofi, and lead co-author of the paper in Science.
The trispecific antibody was tested in an experiment involving monkeys and 2 strains
of SHIV. One SHIV strain is sensitive to neutralization by VRC01 and the trispecific antibody but resistant to neutralization by PGDM1400. The other strain is sensitive to neutralization by PGDM1400 and the trispecific antibody but resistant to neutralization by VRC01. Researchers infused VRC01, PGDM1400 and the trispecific to 3 groups of 8 monkeys. After 5 days, scientists exposed all 24 monkeys to both SHIV strains.Five of the 8 monkeys that received PGDM1400, and 6 of the 8 monkeys that received VRC01 became infected but 0 of the monkeys that received the trispecific antibody became infected.
The antibodies’ ability to target different regions of the virus, which can mutate rapidly, prevented the development of infection, researchers believe.
Plans are under way to conduct early-phase clinical trials of the “trispecific” antibody in healthy people and in people living with HIV in the hope that it could eventually be used for long-acting HIV prevention and treatment. Sanofi is manufacturing the trispecific antibody for use in a Phase 1 clinical trial that will be conducted by NIAID to test the antibody’s safety and pharmacokinetics in healthy people beginning in late 2018.
“Combination therapy has already demonstrated its value in HIV and cancer therapy. Trispecific antibodies represent a potential new class of therapeutics that can block multiple targets with a single agent. This new approach supports a central pillar of Sanofi’s strategy to use multi-targeting to develop transformative medicines for incurable diseases,” said Dr. Nabel.
“At Sanofi, we understand that no single company can conquer major public health threats on its own. By joining forces, the public and private sectors can accelerate our efforts and likelihood of success against infectious diseases and cancer,” said Elias Zerhouni, M.D., President, Global R&D, Sanofi. “We are committed to working collaboratively to develop innovative health solutions.”
