A team at The Scripps Research Institute has come up with a faster way to analyze the outcome of experimental vaccines against HIV and other pathogens. Their new system lets scientists quickly assess the full spectrum of antibodies produced in an individual in response to a pathogen or vaccine and determine if these antibodies are likely to be effective against the pathogen.
With the new study, scientists finally have a way to get a nearly real-time picture of antibody evolution. The new technique builds on Scripps Research-led breakthroughs in immunology and an imaging technique called electron microscopy, which reveals the structures of antibodies bound to their target pathogens, such as HIV.
“We can now watch antibody responses evolve almost in real time,” says Lars Hangartner, PhD, a Scripps Research associate professor and co-senior author of the study
According to Andrew Ward, PhD, professor at Scripps Research and study co-senior author, this technique can be applied to any pathogen. Ward is also affiliated with the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at Scripps Research.
The researchers used rabbit blood samples collected at different stages of an HIV vaccine trial. The researchers purified the samples, breaking down the molecules until they could extract antibody fragments. They then mixed these antibody fragments with their targets – viral proteins – and imaged them in the electron microscope, revealing how the immune system was developing its attack on the pathogen.
This new method is based on images taken by a relatively low-tech method called negative stain imaging, which helped them spot promising, or more often than not, distracting, antibodies. At last, the researchers could quickly find out if a vaccine was pushing the immune system along the right path. And in cases where a vaccine wasn’t working, the method could provide researchers with information as to how the vaccine could be improved.
For an even closer look at the antibodies, Ward used higher-tech cryo-electron microscopy to get high-resolution, 3-D images of the antibodies with their viral targets. These detailed snapshots revealed additional details that may help scientists improve future experimental HIV vaccines.
The researchers say their faster method could open the door to personalized design for vaccines. For example, this study included a “high-responder” rabbit that produced many effective antibodies, and a “low-responder” rabbit with a weak army of antibodies. Going forward, researchers could use this new method in human vaccine or therapeutic trials to quickly separate high responders from low responders early on, saving crucial time for patients and their doctors as they search for effective therapies and vaccines that provide herd immunity.
The Scripps Research Institute (TSRI) is a nonprofit medical research facility that focuses on research and education in the biomedical sciences. Headquartered in San Diego, California (USA) with a sister facility in Jupiter, Florida, the institute has 250 laboratories employing 2,400 scientists, technicians, graduate students, and administrative and other staff, making it the largest private, non-profit biomedical research organization in the USA and among the largest in the world.