Scientists and researchers have reached an important milestone in the fight against HIV. An experimental vaccine developed by scientists at Scripps Research and the nonprofit research organization IAVI has shown promise by eliciting antibodies that have proven effective in neutralizing a wide variety of strains of HIV.
The promising results were recently published in the journal Immunity.
“It’s an initial proof of principle but an important one,” said Richard Wyatt, PhD, a professor in the Department of Immunology and Microbiology at Scripps Research, and the study’s senior author. “We’re now working to optimize this vaccine design.”
Effective vaccines for HIV have been extremely difficult to develop based in large part to the rapid mutation rate as well as other mechanisms employed by the virus for evading immune attack. These mutations mean that a vaccine that shows promise against one strain will often prove ineffective against another.
As a result, it has been widely assumed among vaccine designers that at last two critical sites on the virus must be targeted. The tests in this recent study found that certain “broadly neutralizing” antibodies, or bnAbs, were effective at binding to two specific sites which do not vary significantly from the various mutations.
BnAbs are often produced naturally by the body in some people living with HIV, but not in significant enough numbers or in a timely manner that would prove effective.
The researchers designed a virus-mimicking protein based on HIV’s Env protein. The Env protein spreads out in a bush-like manner on the surface of each HIV particle, and then break into healthy cells by binding to a receptor known as CD4. Researchers engineered a version of Env that was stable enough to use as a vaccine for testing in rabbits. Their tests identified two distinct types of bnAbs that show promise. The first, known as E70, blocks the CD4 binding site while the second, known as 1C2, destabilizes Env to the point it is no longer effective in mediating the entry of HIV into healthy cells.
Ward believes the testing shows it is possible to develop a vaccine using bnAbs to attack the virus. The team intends to refine and improve their strategies in small animals before eventually moving on to testing in monkeys with the ultimate goal of human trials.
Viktoriya Dubrovskaya, PhD, and Gabriel Ozorowski, PhD, of Scripps Research and Karen Tran, PhD, of the IAVI Neutralizing Antibody Center at Scripps Research, were co-lead authors of the study entitled “Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability.”
Also contributing was Andrew Ward, PhD, a professor in the Department of Integrative Structural and Computational Biology at Scripps Research, researchers at the University of Southampton, UK, the National Institute of Allergy and Infectious Diseases in Maryland, the Karolinska Institutet in Stockholm, and the Fred Hutchinson Cancer Research Center in Seattle.