A laboratory-made experimental antibody can completely prevent non-human primates from becoming infected with the monkey form of HIV, according to new research published in Communications on Nature shows.
The results will report a future human clinical trial that will evaluate leronlimab as a potential pre-exposure prophylaxis, or PrEP, therapy to prevent human infection with the virus that causes AIDS.
“The results of our study indicate that leronlimab could be a new weapon against the HIV epidemic,” said the study’s lead researcher and corresponding author of this article, Jonah Sacha, Ph.D., professor from Oregon Health and Science University to the OHSU Oregon National Center for Primates and Institute for Gene Therapy and Vaccines.
“The results of this pre-clinical study, aimed at the CCR5 of the HIV co-receptor, can be innovative, as we essentially have a tool that can mimic the genetic mutations of CCR5 that make some individuals immune to infection and have given in part two cases of cure of HIV, ”said the other corresponding author, Lishomwa Ndhlovu, MD, Ph.D., professor of immunology in medicine at Weill Cornell Medicine in New York City.
Manufactured by CytoDyn, based in Vancouver, Washington, the monoclonal antibody blocks the entry of HIV into immune cells through a surface protein called CCR5. He injectable drug has already been studied in a phase 3 trial as a potential treatment for people with HIV when used in combination with standard antiretroviral drugs. CytoDyn is sending information to the FDA to request its approval for this use. This study, however, specifically examined the prevention of HIV infection to begin with.
Some PrEP medications are already available, but they can cause adverse 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 often require frequent use, such as a daily pill, or are infusions to be administered in a clinic. Leronlimab is designed to be a self-administered injection.
To study the effectiveness of leronlimab as a potential PrEP drug, the research team created three groups of six rhesus macaques at the Oregon National Primate Research Center, OHSU. Two groups received different doses of leronlimab, while the third served as a control that did not receive the experimental drug.
The macaques receiving the highest dose of 50 milligrams per kilogram of animal weight every two weeks were completely protected from the monkey form of HIV. In contrast, two of the animals receiving the lower dose of 10 milligrams per kilogram per week became infected and all animals in the control group became infected. The researchers concluded that the partial protection of the group with low doses is probably due to the immune responses of monkeys against human antibody.
Following the results of this study, CytoDyn plans to conduct an early clinical trial investigating leronlimab as a potential PrEP drug in people next year. Doses in humans would likely be lower than those given in this study, as rhesus macaque cells have more superficial CCR5 protein than humans.
Meanwhile, Sacha is already trying to make leronlimab easier to use. He received a five-year, three-million-dollar NIH grant in August 2020 to develop a concentrated and more durable formulation of leronlimab that could allow its injection every three months. Less frequent injections may increase adherence to the pharmacological regimen and therefore improve the efficacy of the drug.
The research team dedicated this study to Timothy Ray Brown, who died on September 29, 2020 and was 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 to treat his blood cancer. The procedure removed HIV from Brown because the transplanted bone marrow came from a donor with a rare mutation that deleted the CCR5 gene, which causes the surface protein through which HIV enters cells. Sacha befriended Brown after meeting him at an AIDS conference in 2015. Brown is also a co-author of the paper and inspired scientists working on this research.
Xiao L. Chang et al, antibody-based CCR5 blockade protects macaques from mucosal SHIV transmission, Communications on Nature (2021). DOI: 10.1038 / s41467-021-23697-6
Oregon Health & Science University
Citation: Monoclonal Antibody Prevents HIV Infection in Monkeys, According to Study (2021, June 7), Retrieved June 7, 2021 at https://medicalxpress.com/news/2021-06-monoclonal-antibody -hiv-infection-monkeys.html
This document is subject to copyright. Apart from any fair treatment for the purposes of private study or research, no part may be reproduced without written permission. Content is provided for informational purposes only.