Laboratory-made experimental antibody may completely prevent non-human primates from becoming infected with the monkey form of HIV, new research shows published in Nature Communication shows.
The results will inform a future human clinical trial evaluating leronlimab as a potential pre-exposure prophylaxis therapy, or PrEP, to prevent human infection with the virus that causes AIDS.
“The results of our study indicate that leronlimab may be a new weapon against the HIV epidemic,” said study principal investigator and co-author of this article, Jonah Sacha, Ph.D., professor at Oregon Health & Science University at OHSU’s Oregon National. Primate Center and Institute for Vaccination and Gene Therapy.
“The results of this preclinical study, targeting the HIV co-receptor CCR5, have the potential to be groundbreaking because we essentially have a tool that can mimic the genetic mutations in CCR5 that render some individuals immune to infection and have led to partly to two cases of healing from HIV, ”said other co-correspondent author Lishomwa Ndhlovu, MD, Ph.D., professor of medical immunology at Weill Cornell Medicine in New York City.
Manufactured by CytoDyn, based in Vancouver, Washington, the monoclonal antibody blocks HIV from entering immune cells through a surface protein called CCR5. The injectable drug has already been studied in a phase 3 trial as a potential treatment for people living with HIV when used in combination with standard antiretroviral drugs. CytoDyn is in the process of submitting information to the FDA to seek approval for this use. This study, however, looked specifically at preventing HIV infection to begin with.
Some PrEP drugs are already available, but they can cause unwanted side effects such as liver, heart and bone problems, and some people are resistant to them due to genetic mutations in HIV. Existing PrEP options usually require frequent use, such as one pill a day, or are infusions that must be given in a clinic. Leronlimab is designed to be a self-administered injection.
To study the effectiveness of leronlimab as a potential drug for PrEP, the research team created three groups of six rhesus macaques at the Oregon National Primate Research Center of OHSU. Two groups received different doses of leronlimab, while the third served as a control that did not receive the investigational drug.
Macaques that received the highest dose of 50 milligrams per kilogram of animal body weight every two weeks were completely protected from the monkey form of HIV. In contrast, two of the animals that received the lower dose of 10 milligrams per kilogram per week were infected and each animal in the control group was infected. The researchers concluded that the partial protection of the low-dose group was likely due to the monkey’s immune responses to the human antibody.
Following the results of this study, CytoDyn plans to conduct an early clinical trial of leronlimab as a potential drug for PrEP in humans within the next year. Human doses would likely be lower than those given in this study because rhesus macaque cells have more surface CCR5 protein than humans.
In the meantime, Sacha is already trying to facilitate the use of léronlimab. It received an NIH grant of $ 3 million over five years in August 2020 to develop a concentrated and more durable formulation of leronlimab that could allow it to be injected every three months. Less frequent injections can increase adherence to the drug regimen and therefore improve the effectiveness of the drug.
The research team dedicated this study to Timothy Ray Brown, who died on September 29, 2020 and is known as the Berlin patient for being the first person to be cured of HIV. While living in Berlin in 2007, Brown underwent a bone transplant the next day to treat his blood cancer. The procedure eliminated HIV at Brown because the transplanted bone marrow came from a donor who had a rare mutation that knocked out the CCR5 gene, which is the surface protein through which HIV enters cells. Sacha became friends with Brown after meeting him at an AIDS conference in 2015. Brown is also a co-author of the article and has inspired scientists working on this research.