Early Infusion of Antibody Therapy Induces Long-Last Immune Response to SHIV

Administering 2 anti-HIV antibodies immediately after infection enables durable control of the virus, a new study suggests.

In the study, published in Nature, investigators used 13 macaque monkeys inoculated with the simian-human immunodeficiency virus (SHIV), and gave them 3 intravenous infusions of the antibodies—3BNC117 and 10-1074—over a 2-week period.

The results of the study showed that the treatment suppressed the virus to levels near or below the limit of detection, and the effect lasted for as long as 6 months. Once the antibodies had been cleared out of the animals’ bodies, the SHIV rebounded in all the monkeys except 1.

Interestingly, 5 to 22 months later, the investigators observed that 6 of the monkeys spontaneously regained control of the virus, and once again their viral levels plummeted to undetectable levels and remained suppressed for another 5 to 13 months.

After receiving the antibody infusions, the 6 monkeys maintained healthy levels of key immune cells, according to the study. Furthermore, 4 additional monkeys that did not regain complete control of the virus showed promising responses to the treatment.

The 4 monkeys maintained extremely low viral loads and healthy levels of key immune cells for 2 to 3 years after infection. Overall, 10 of 14 monkeys benefitted from the antibody immunotherapy.

The investigators also sought to determine which aspects of the immune system helped the monkeys stave off the return of the virus. The 6 controller monkeys were infused with an antibody that targets and depletes cytotoxic T cells. When the antibody was infused, the SHIV levels in the monkey’s blood immediately increased, while cytotoxic T cell levels decreased, indicating that the cells play a key role in preventing SHIV replication after therapeutic antibody infusion.

Although SHIV does not precisely mimic human HIV, the findings suggest the need for immunotherapy to be explored as a way of controlling the virus and boosting an immune response to control the infection in humans.

“This form of therapy can induce potent immunity to HIV, allowing the host to control the infection,” said investigator Michel Nussenzweig. “It works by taking advantage of the immune system’s natural defenses, similar to what happens in some forms of cancer immunotherapy.”

The experiment is now being replicated after a longer exposure to the virus. Instead, the investigators will wait 2 to 6 weeks after SHIV infection before administering the antibody infusions, because this is how long it typically takes for a individual infected with HIV to be diagnosed and become eligible to receive treatment.

Human clinical trials testing the antibody combination are also underway at The Rockefeller University Hospital.