Novel Antibody Clinical Study to Inform Development of HIV Immunoprophylaxis

MHRP, through an international collaboration, just launched a new study (RV584) in Tanzania to test novel long-acting bispecific antibody alone and in combination with another potent monoclonal antibody (mAb) to determine and compare safety and antiviral effects, or how effective these drugs are at reducing the amount of HIV in people living with HIV, both alone and in combination.

“This study will inform countermeasures that can potentially be used to mitigate HIV risk to the battlefield blood supply in pre- and post-exposure prophylaxis settings,” according to MHRP director COL Julie Ake.

The bispecific antibody 10E8.4/iMab will be tested alone as an infusion at different doses and as an injection into muscle, or in combination with the mAb VRC07-523LS as an infusion. This study will not only help researchers understand how these drugs might be useful for preventing or treating HIV, but will also explore the safety of intramuscular injections of mAbs, which if found to be safe, would greatly expand the feasibility of using them to prevent and possibly treat HIV.

The products being used, 10E8.4/iMab and VRC07-523LS, are designed to synergistically target the HIV virus and its binding site on human CD4 lymphocytes. The bispecific antibody (10E8.4/ iMab) was developed by the lab of Dr. David Ho, the director of the Aaron Diamond AIDS Research Center at Columbia University in New York City. Bispecific antibodies (bsAbs) are engineered antibodies that contain two different antigen-binding sites in one molecule. The two components of 10E8.4/iMab include Ibalizumab, which is specific to CD4 and is already approved for treatment-resistant HIV, and 10E8.4, a very broad monoclonal antibody that targets the membrane-proximal external region of the HIV envelope. The bispecific antibody is very potent and active against a wide range of HIV virus variants because it is designed to focus the activity of the antibody at the precise location where it is needed. Dr. Ho is also serving as the RV584 study sponsor.

VRC07-523LS, a highly potent and broadly neutralizing monoclonal antibody that targets the HIV-1 CD4 binding site, was developed at the U.S. National Institutes of Health (NIH) Vaccine Research Center. It has been shown to be active against 96% of diverse HIV-1 strains. MHRP is testing both drugs in this research study to see if this combination is safe and more effective at reducing volunteers’ viral load.

COL Ake added that “the research team plans to leverage our existing partnerships and international network to recruit volunteers from health care facilities with very high patient populations in Mbeya which are supported by MHRP’s PEPFAR program.”

RV584 will enroll participants from the Mbeya Regional and Zonal Referral Hospitals with local research leadership provided by Tanzania’s National Institute of Medical Research - Mbeya Medical Research Center. Dr. Marco Missanga is the principal investigator of the study, which is funded by the DoD through MHRP.