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 have used them to provoke an immune response in animals.
Their work, which was published recently in the journal Cell Reports, could advance the design of an effective AIDS vaccine.
The researchers successfully produced synthetic nanoparticles (liposomes) 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 team leader Richard Wyatt, professor of immunology at the IAVI Neutralizing Antibody Center at TSRI.
“It turns out that this was indeed the case,” said TSRI Research Associate Jidnyasa Ingale. “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."
Authors of the new study include (left to right) Richard Wyatt, Michael Zwick, Armando Stano and Jidnyasa Ingale. (Photo by Cindy Brauer.)
The researchers tested the trimer-containing particles in animal models, finding that they successfully and efficiently provoked the immune system to respond. Specifically, the particles activated B cells, white blood cells 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.
In addition to Wyatt and Ingale, authors of the Cell Reports paper, “High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells,” are Armando Stano, Javier Guenaga, Shailendra Kumar Sharma, David Nemazee and Michael Zwick.
This work was funded by the National Institute of Allergy and Infectious Diseases (NIAID) HIV Vaccine Research and Design Program (grant P01 AI104722), NIAID Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (grants AI100663, R01AI073148 and AI098602) and IAVI and its generous donors.
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