One Antibody Dose Kept an HIV-Like Virus in Remission in Infant Monkeys

A single dose of an experimental antibody, given alongside early antiviral treatment, kept simian immunodeficiency virus (SIV), a relative of HIV, from returning for months in infant macaques, and for four years of follow-up in one animal. The study by a team including virologist Jesse Deere and immunologist Dennis Hartigan-O'Connor at the University of California, Davis, was published online on October 19 in Nature Microbiology.

The hidden reservoir

HIV and SIV can fall silent without leaving the body. They insert their genetic material into the DNA of immune cells and then lie dormant without producing new virus. These cells form a latent viral reservoir. Antiretroviral drugs stop the virus from multiplying but cannot clear it from these cells, and without viral proteins on their surface the cells are hard for the immune system to recognise. When the drugs are stopped, the virus can start multiplying again.

Instead of searching for each infected cell, the team targeted a broader group of cells that carry a surface protein, C-C chemokine receptor type 5 (CCR5), which the viruses can use to enter cells. Their antibody binds both CCR5 and CD3, a protein complex on T cells, and so directs T cells to attack cells carrying CCR5, including cells that may harbour the virus and cells it could infect later.

How the experiment worked

The researchers exposed 25 newborn rhesus macaques to SIV; 20 became infected. A week after infection the animals began antiretroviral treatment, which continued for 18 weeks and was then stopped to see whether the virus returned. The animals had been randomly assigned to three groups: drugs alone, drugs plus a single dose of the CCR5/CD3 antibody (started two days after the drugs), or drugs plus a different antibody that targets a cell-surface protein called CD4.

In every animal given drugs alone, the virus reappeared in the blood within a week. In the CD4-antibody group, six of eight animals rebounded within seven days, while one stayed free of detectable virus through the end of follow-up. Some recipients of the CCR5/CD3 antibody stayed in remission much longer: four showed no sign of the virus in the blood for more than three months, in two it returned after 97 and 173 days, a third had no rebound before follow-up ended at around 29 weeks, and in the longest-followed animal the period reached four years.

Is the virus gone?

Remission here means a prolonged absence of detectable virus after medication ends; by itself it does not show the infection has been cleared. The team ran further tests on three animals in sustained remission, two of which had received the CCR5/CD3 antibody. When they temporarily depleted CD8 T cells, which help control viral infections, no rebound occurred. Tissue tests found no viral genetic material, and attempts to recover infectious virus from lymph-node cells failed. One sample from the animal followed for four years produced a tiny signal of possible viral RNA; the researchers could not exclude contamination and found no viral DNA or return of virus in the blood.

Caveats

The study was small, and treatment began soon after infection. The team used infant monkeys partly because they can rebuild immune cells quickly, so it is unknown whether the approach would work in adults or in long-standing infections. The antibody also targets uninfected immune cells; the animals generally tolerated it, with mild reactions that resolved within hours, but effects on defences against other infections need study. "Our study demonstrates that targeting CCR5-expressing cells using the host immune system may be a surprisingly effective route to HIV cure, at least for infants that can be treated soon after infection," the authors conclude. The approach has not been tested in people. More in our Health section.