Newswise — David Peabody, PhD, and Bryce Chackerian, PhD, are creating vaccines from particles that are the opposite of Trojan Horses: they look deadly on the outside but are harmless on the inside.
The idea, says Peabody, is to trick the body into believing it’s been infected with a microscopic foe. The body’s reaction to the supposed infection prepares it for an assault by the real foe.
Scientists at The University of New Mexico, Peabody and Chackerian are using a one-year $250,000 grant to make a vaccine to protect against COVID-19 using the virus-like particles that they developed.
The spherical particles are produced by bacteria and can be made to look like anything dangerous: a parasite, a cancer cell, a virus. Peabody can genetically engineer the particles to display a part of the parasite’s, cell’s or virus’ surface proteins — the part is called an epitope — on the outside. The repeating epitope pattern incites the immune system to react strongly and form antibodies against the epitope.
Decorating the outside of virus-like particles with epitopes isn’t enough to ward off disease, though. Antibodies are as uniquely shaped as the epitopes to which they bind. Chackerian explains that not all antibodies will stop a virus.
“For viral vaccines, the goal is to produce neutralizing antibodies,” he says. “This is an antibody that can attach to the virus and then effectively prevent the virus from infecting a cell.”
To make a vaccine against COVID-19, Chackerian and Peabody are using knowledge of the genome of the SARS-CoV-2 virus, which causes the respiratory disease.
Peabody summarizes, “We make a virus-like particle that displays on its surface bits of SARS-CoV-2. And if those bits of SARS-CoV-2 elicit antibodies that neutralize the virus, that’s a vaccine.”
Peabody and Chackerian say they can make vaccine candidates quickly and they have a system that can direct the immune system to respond to specific epitopes. Previously, their virus-like particles have been used to make vaccines to target human papillomavirus, malaria, and even metastatic breast cancer cells.
“The goal,” says Chackerian, “would be to develop a vaccine that would develop strong and long-lasting responses to the parts of the virus that are critical for its function.”
Peabody and Chackerian don’t know the specific parts of the SARS-CoV-2 virus to target, but they can make educated guesses. In addition to the genome sequence of the SARS-CoV-2 virus, they have information about how people’s immune systems responded to a similar virus during the SARS outbreak in 2003. Peabody says that the two viruses are structurally similar enough that they likely share critical epitopes.
But each vaccine candidate will need to be tested for its ability to elicit antibodies that block virus entry into a cell. Testing requires time and a scientific team. Peabody and Chackerian’s team includes Steven Bradfute, PhD, at the UNM Center for Global Health, and Kathryn Frietze, PhD, and Alison Kell, PhD, at UNM’s Department of Molecular Genetics and Microbiology.
To make a pipeline of possible vaccines, Peabody and Frietze select potential epitope targets and engineer the virus-like particles. Chackerian vaccinates test animals and collects blood samples from them. He and Kell are also conducting studies to confirm that the vaccines actually bind to their intended cellular targets. And, Bradfute is testing blood samples from the animals to verify that their antibodies block infection.
This work and these tests take place before clinical trials. Once a vaccine candidate is successful in a clinical trial, though, Peabody and Chackerian plan to work with a partner and expect to produce large amounts of vaccine in a short time.
Clinical trials, however, can take years to ensure safety and efficacy. But Peabody and Chackerian see another advantage the virus-like particles can offer.
“We imagine a world in which there’s a platform technology that’s pre-approved for use [in humans], with interchangeable parts that you trade out to correspond to whatever threat you’re trying to address,” says Peabody. “[So] that adding another epitope from a different agent will be approved more quickly than if you have to start entirely from scratch.”
David Peabody, PhD, is a Professor in the Department Molecular Genetics and Microbiology at the UNM School of Medicine and a member-at-large of the UNM Comprehensive Cancer Center.
Bryce Chackerian, PhD, is a Professor and the Vice Chair of the Department of Molecular Genetics and Microbiology at the UNM School of Medicine and a full member of the UNM Comprehensive Cancer Center.
The National Cancer Institute of the National Institutes of Health is supporting the research reported in this publication under Award Number P30CA118100-15S5. Principal Investigator: David Peabody, PhD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.