Broadly Neutralizing Antibodies May Lead to HIV Vaccine

Engineered immunogens incite the immune system to produce antibodies that show promise for an HIV vaccine.

Broadly neutralizing antibodies were found to prevent HIV infection in a recent study, offering hope for an upcoming HIV vaccine clinical trial that can induce these antibodies.

This vaccine strategy immunizes individuals using a series of differently-engineered immunogens that incite the immune system to produce broadly neutralizing antibodies. In order for this vaccine strategy to be successful, the first immunogen needs to have the ability to bind and activate precursor B cells, according to the study.

The, study published in Science, found that precursor (germline) cells for one kind of broadly neutralizing HIV antibody are present in a majority of patients, and the design of an HIV vaccine germline-targeting immunogen is capable of binding to the B cells.

“We found that almost everybody has these broadly neutralizing antibody precursors, and that a precisely engineered protein can bind to these cells that have potential to develop into HIV broadly neutralizing antibody-producing cells, even in the presence of competition from other immune cells,” said lead study author, William Schief.

Although the human immune system has a large amount of different precursor B cells, it is rare for the cells to have the ability to recognize a specific part of the virus surface within the group of precursor B cells.

“The challenge for vaccine developers is to determine if an immunogen can present a particular viral surface in a way that distinct B cells can be activated, proliferate and be useful,” said study co-author Shane Crotty. “Using a new technique, we were able to show -- well in advance of clinical trials -- that most humans actually have the right B cells that will bind to this vaccine candidate. It is remarkable that protein design can be so specific as to 'find' one in a million cells, demonstrating the feasibility of this new vaccine strategy.”

The upcoming phase 1 clinical trial will test a nanoparticle version of an engineered HIV vaccine protein called eOD-GT8 60mer. The study will test the safety, efficacy, and ability of the protein to elicit an immune response that mimics the beginning of broadly neutralizing antibody development.

“Data from this new study was also important for designing the clinical trial, including the size and the methods of analysis,” Schief said.

Back in June, researchers found that eOD-GT8 60mer produced an antibody response in mice and showed some of the necessary traits needed to recognize and inhibit HIV. If researchers find similar results in human trials, it suggests that additional boost immunogens are needed to induce the antibodies that block HIV.