A Next Step in the bnAb Journey

By: Gail Broder, HVTN Core, Seattle, WA, USA
with contributions from the HVTN 127/HPTN 087 Protocol Team

Antibodies are one of the natural ways that our bodies fight infection. Giving people antibodies to prevent infection is an accepted medical practice more than 100 years old. For example, doctors give people antibodies to prevent infections like hepatitis A and B and chicken pox. Some antibodies that are used for preventing infections are made in laboratories. Manufactured antibodies have been used to prevent a dangerous respiratory infection in infants called Respiratory Syncytial Virus (RSV), and to prevent and treat diseases such as rheumatoid arthritis and breast cancer.

In the HVTN, we began working with broadly neutralizing antibodies (bnAbs) a few years ago. bnAbs are special antibodies that seem to recognize many strains of HIV from across the globe. In lab tests, they are able to attach onto the surface of HIV and block it from being able to attach to a person’s cells to cause an infection. The HVTN first tested passive administration of bnAbs in HVTN 104, and is now working with the HIV Prevention Trials Network (HPTN) to do the AMP Studies, the first efficacy studies to see if one particular bnAb called VRC01 can prevent HIV infection in people.

The next bnAb we are testing is called VRC07-523LS, and once again we are joining forces with the HPTN to conduct the clinical trial. HVTN 127/HPTN 087 is a phase I study that is looking at 3 different doses of the antibody, and also three different ways of giving the antibody. This antibody has been engineered in the lab to make it last longer in the body and to make it better able to neutralize even more strains of HIV, possibly at even lower doses than VRC01. Volunteers will get the antibody 5 times, once every 4 months. Some people will get it by an intravenous (IV) drip, some will get it by a sub-cutaneous injection (a shot under the skin), and others will get it by a shot in the muscle of the upper arm or in the butt, whichever is preferred. In addition to looking at safety and whether participants are able to get the antibody without being too uncomfortable, this study will also look at how much of the antibody remains in the human body over time, if the immune system responds to the antibody, and if those immune responses are different depending on the dose or how the antibody is given to people.

The study opened in January, 2018, and will enroll 124 people. The study is being done at HVTN and HPTN sites in Lausanne, Switzerland; Atlanta, GA; Birmingham, AL; Boston, MA (2 clinics); Chapel Hill, NC; and New York, NY.

* Gail Broder is a Senior Community Engagement Project Manager for the HVTN, and a protocol team member for HVTN 127/HPTN 087.