Call it a sheep in wolf's clothing. Researchers with the International Aids Vaccine Initiative (IAVI) and The Scripps Research Institute (TSRI) have built tiny particles that resemble HIV on their outside and used them to provoke an immune response in animals. Their work, which was published today in the journal Cell Reports, could advance the design of an effective AIDS vaccine.
The researchers successfully produced synthetic nanoparticles (liposomes) that they decorated with protein components (trimer spikes), that protrude from HIV-1's outer membrane (the viral envelope). These protein components are normally used by the virus to grab onto the human cells it then goes on to infect.
HIV has roughly a dozen of the trimer spikes on its envelope surface. In contrast, the synthetic nanoparticle is decorated with several hundred spikes that mimic the native trimers. “We built the nanoparticle envelope with this many spikes because we thought it would offer a real advantage to trigger a more effective immune response by offering the immune system more binding sites ,” said Richard Wyatt, the senior author of the study and an immunology professor at IAVI's Neutralizing Antibody Center at TSRI.
“It turns out that this was indeed the case. We've found that the trimer-liposomes better elicits an immune response than trimers that are not packaged on such particles. This establishes our technique as a potential first step toward a more broadly effective vaccine against HIV,” said Jidnyasa Ingale the lead author and Research Associate at TSRI.
The researchers tested the trimer-containing particles in mice and rabbits, finding that it successfully and efficiently provoked the immune system to respond. Specifically, the particles activated B cells, a white blood cell that can produce broadly neutralizing antibodies, which, in laboratory tests, have shown that they are able to neutralize a broad spectrum of the many HIV-1 variants that circulate globally. HIV-1 is the most widespread HIV type worldwide.
The researchers say their early success doesn't just hold opportunity for HIV. The approach of building synthetic pathogen mimics could possibly be used to make vaccines against other types of viruses, as well.