Immune Cell "Precursors" to HIV Antibodies Could Lead to Vaccine
Scientists had all but given up on the idea of developing a vaccine that elicits antibodies which specifically neutralize HIV.
“An emerging vaccine strategy involves immunizing people with a series of different engineered HIV proteins as immunogens to teach the immune system to produce broadly neutralizing antibodies (bnAbs) against HIV,” The Scripps Research Institute reports in a news release. “This strategy depends on the ability of the first immunogen to bind and activate special cells, known as broadly neutralizing antibody precursor B cells, which have the potential to develop into broadly neutralizing antibody-producing B cells.”
Now scientists have found that most people can produce immune cell “precursors” to antibodies that will fight HIV, and are hoping this may be the answer to an effective HIV vaccine.
In a study published today in Science, researchers from Scripps, the International AIDS Vaccine Initiative and La Jolla Institute for Allergy and Immunology say they have found the right precursor “germline” cells for one kind of HIV bnAbs that is “present in most people,” according to the news release, “and has described the design of an HIV vaccine germline-targeting immunogen capable of finding those B cells.”
In fact, a Phase 1 clinical trial already is being planned to test a nanoparticle (tiny) version of the engineered HIV vaccine protein, known as the “eOD-GT8 60mer.”
“We found that almost everybody has these broadly neutralizing antibody precursors, and that a precisely engineered protein can bind to these cells that have the potential to develop into HIV broadly neutralizing antibody-producing cells, even in the presence of competition from other immune cells,” said the study’s lead author, Williams Schief, TSRI professor and director, Vaccine Design of the IAVI Neutralizing Antibody Center at TSRI. “The goal of the clinical study will be to test safety and the ability of this engineered protein to elicit the desire immune response in humans that would look like the start of broadly neutralizing antibody development.”
In June, scientists reported that eOD-GT8 60mer produced antibody responses in mice “that showed some of the traits necessary to recognize and inhibit HIV. If the eOD-GT8 60mer performs similar in humans, additional boost immunogens are thought to be needed to ultimately induce broadly neutralizing antibodies that can block HIV.”
“The interaction of the naive human B cell repertoire with vaccine antigens has not been characterized previously,” the researchers concluded in their paper. “Given the vast immunoglobulin sequence space, direct probing of the human naïve B cell repertoire was a critical test of the physiologically relevant binding potential of the germline-targeting immunogen.”
In other words, it was important to find out whether naïve B cells could even bind to HIV-specific immunogens (such as VRC01) and be effective.
“The antibody sequence features, binding affinities, and high structural similarity of the eOD-GT8-specific naïve B cell derived antibodies to VRC01 all demonstrate the power of germline-targeting design when combined with human B cell probing. Similar methods, including both protein design and human B cell probing methods, could be used to improve and evaluate germline-targeting immunogens for other classes of HIV bnAbs and for Abs against other pathogens.”