A Step Closer to an Effective HIV Vaccine

In a significant HIV milestone, researchers have learned how to stimulate the immune system in animal models to produce large quantities of broadly neutralizing antibodies against the human immunodeficiency virus—a prerequisite for an effective vaccine against HIV.

“We still have much to do before we can make a vaccine for humans, but we’ve shown it’s possible to reproducibly induce the antibody response needed to neutralize HIV,” says study leader Peter Kwong, PhD, the Richard J. Stock Professor of Medical Sciences and professor of biochemistry & molecular biophysics at Columbia University Vagelos College of Physicians and Surgeons. (Kwong was formerly chief of the Structural Biology Section at the Vaccine Research Center at the National Institutes of Health, where most of the research was conducted).

The two-step approach uses vaccination with a conserved part of HIV to trigger B cells to produce broadly neutralizing antibodies, followed by infection with a modified form of the virus. “The first step stimulates the immune system to create broadly neutralizing antibodies, which recognize a wide range of HIV strains. The second step—infection—demonstrated that high titers could be achieved, though in an unusual way, with only one to a few B cell lineages providing for all the neutralization,” explains Kwong.

The study was published in the Dec. 12 issue of Cell.

About 15 years ago, hopes for an HIV vaccine were raised when researchers discovered that some people infected with HIV naturally produce effective antibodies that block a wide range of HIV strains from entering healthy cells. But reproducing such antibody responses with conventional vaccine approaches has failed.

More recently, Kwong and his colleagues demonstrated in an animal model of HIV that vaccination with a critical part of the HIV spike protein called ‘fusion peptide’ could reliably trigger the immune system to make broadly neutralizing antibodies. (Fusion peptides are also critical parts of the COVID virus spike and used by both COVID virus and HIV to enter human cells).

“While the vaccine could produce a broad antibody response, the titers—or numbers—of antibodies just weren’t high enough,” says Kwong.

The researchers tried many ways to boost the response, including additional immunizations with fusion peptide, alone or in combination with the complete viral spike. They also tried various adjuvants (molecules that enhance vaccine responses) and different vaccination schedules. None of these tactics worked.

The natural way that broadly neutralizing antibodies are stimulated in humans is through infection, so Kwong and his team mimicked this through a vaccine plus virus strategy. This approach was successful and elicited high titers of broadly neutralizing antibodies that were capable of neutralizing 45% to 77% of a panel of 208 HIV strains.

“We’ve finally established proof of principle that we can consistently induce the high titer responses needed to neutralize HIV,” says Kwong.