Immature HIV Antibody May Lead to Improved Treatments

Rare effective antibodies taken from HIV patients serve as guides to reverse engineer optimal vaccine candidates.

The first-ever immature anti-HIV antibody has been discovered and could help future developments of AIDS vaccinations, according to a recent study.

HIV has the ability to mutate rapidly and its set of defenses — including a shield of glycan molecules – prevents scientists from using traditional methods to create a vaccine. A study published in Immunity used rare effective antibodies from HIV patients as guides to reverse engineer the correct vaccine candidates.

“This is actually the first example of how we can go back to the really early stage to see how this antibody lineage was born and can develop,” said co-senior study author Jiang Zhu.

The antibody used was taken from a patient in China with an immune system that created antibodies that are VRC01-like with the ability to fight HIV. Scientists’ referred to it as an elite controller.

However, the antibody lacked 1 of the key structural traits of the VRC01 antibodies.

“There was something a little bit weird about this antibody,” Zhu said.

Upon further examination, researchers found that the antibody was a precursor to mature VRC01 antibodies. Zhu defines it as a “teenager” antibody, and it represents a middle stage in the evolution of this class.

The teenager antibody allows for scientists to gain a unique view of the steps to get the immune system to target HIV. During the study, samples of “toddler” antibodies were taken from patients over 5 years to be examined. Each sample showed the antibody in a different stage of development.

Between 2006 and 2008, the antibody evolved rapidly and gained many of the traits needed to fight HIV.

The findings disprove prior studies that estimate it takes up to 10 to 15 years for VRC01 antibodies to fully develop.

“That was a solid theory, until we saw the antibody from this donor,” Zhu said.

Although the antibodies were found to evolve in just 1 or 2 years, there are some hurdles that researchers are faced with.

The teenage VRC01 has an amino acid chain that’s slightly longer at 1 site compared with the mature antibody. The amino acid chain clashes with part of the glycoprotein shield (gp120) on HIV, preventing the antibody from effectively neutralizing the virus.

This challenge will need to be overcome as researchers continue to engineer their own antibodies.

“As long as you have some of those VRC01 signatures, a teenage-stage antibody can become a killer for HIV,” Zhu said.

Researchers noted that this is the first time a VRC01-like antibody has been isolated from an Asian decent patient. This suggests that different genetic backgrounds could benefit from a vaccine that harnesses an individual’s ability to make VRC01s.

This has the potential to become an important part in the development of a universal HIV vaccine.