Altered Broadly Neutralizing HIV Antibody Potential Major Player in HIV Prevention

With 36.7 million individuals living with HIV worldwide, the virus remains a major threat to public health. However, researchers continue to make strides in the fight against the virus, especially in prevention.

One avenue that researchers have taken to exploring involves anti-HIV antibodies. Researchers have started testing how periodic infusions of these antibodies can work to prevent infection, a process referred to as ‘passive immunization’. One specific antibody, VRC01, has been on researchers’ radar for some time now, as it has been found to be broadly neutralizing, or, effective against several strains of HIV.

VRC01 was first discovered in 2010 by VRC scientists and was found to be able to neutralize a whopping 90% of HIV strains; it did so by binding to the CD4 binding site on the surface of the HIV envelope, preventing the cell for attaching to immune system cells.

Researchers from the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center (VRC) have taken to altering VRC01 in an attempt to preserve its neutralization capability and make it last longer in the blood than traditional antibodies; by doing this, individuals would be protected against the virus for longer periods of time and require less frequent dosing.

The modified version of VRC01 works by “taking advantage of how the body recycles its own antibodies,” according to the authors, so the body will work to protect VRC01LS from being broken down.

The results of the phase 1 study, recently released, look promising.

For the first clinical trial of VRC01LS, the modified version of VRC01, researchers enrolled 37 healthy adults, all HIV-negative, ranging between the ages of 21 and 50 years; 51% of participants were male, and 49% were female, according to study authors.

The primary objectives of the study “were safety and tolerability of VRC01LS intravenous infusions at 5, 30, and 40 mg/kg infused once, 20 mg/kg given 3 times at 12-week intervals, and subcutaneous delivery at 5 mg/kg deliver once, or 3 times at 12-week intervals,” the study authors wrote. “Secondary objectives were pharmacokinetics, serum neutralization activity, and development of antidrug antibodies.”

The researchers found that the modified antibody was safe and as effective as VRC01 at neutralizing multiple strains of HIV. Furthermore, the altered antibody was able to persist in the human body more than 4 times longer than VRC01. Study participants did not experience any serious health consequences either, although some did complain of mild muscle aches and tiredness.

“The reduced clearance and extended half-life may make it possible to achieve therapeutic levels with less frequent and lower-dose administrations,” the study authors concluded. “This would potentially lower the costs of manufacturing and improve the practicality of using passively administered monoclonal antibodies for the prevention of HIV-1 infection.”

Based on these promising results, NIAID scientists and others are working on testing this modification in other broadly neutralizing HIV antibodies in order to create more candidates that can be used in passive immunization.

​​​​​​