Progress in AIDS Vaccine Strategy

Scientists may be one step closer to making a vaccine that could protect people from the human immunodeficiency virus (HIV) according to California researchers who designed a novel array of trimer-presenting nanoparticles with potential vaccine antigens. The study, published in Nature Communications on June 28, 2016, was conducted by Linling He, of the Scripps Institute, and colleagues.

The researchers set out to “investigate the nanoparticle display of trimeric HIV-1 antigens by combining structural and antigenic analyses with B-cell activation assays,” they said. The goal is to design a nanoparticle that can mimic the virus, called a virus like protein (VLP), causing the body to begin producing antigens before a person is exposed to the real virus. The same concept has been successfully used to develop the vaccines used against human papillomavirus (HPV) and hepatitis B.

They designed a structure on which 2 parts of the trimeric “can be presented in native-like conformations around the threefold axes on the surface of nanoparticles,” they explain. They then fuse the third part of the subunit on, saying, “These chimeric antigens can assemble into nanoparticles with high affinity for bNAbs [broadly neutralizing antibodies] targeting the apex, as well as other key epitopes, consistent with native-like trimer conformations.”

Previous research made it clear that VLPs should be a high priority in the development of a vaccine, but the researchers say, “the suboptimal structural and antigenic properties of this nanoparticle highlighted the need for a more in-depth analysis.” The present study provided that analysis and for the first time that nanoparticles can be designed that “provide useful tools to investigate the B-cell responses to the apex and other bNAb epitopes in a multivalent form,” they said.

The research team tested different combinations and found six versions of the trimer that will eventually be tested on animals. The researchers said, “Our study provides an arsenal of multivalent immunogens for HIV-1 vaccine development.”