New Epstein-Barr virus vaccine

Implicated in the onset of cancer, blamed as the cause of mononucleosis and, more recently, in triggering the degenerative nerve disease multiple sclerosis, the Epstein-Barr virus will soon have an innovative vaccine thanks to the research of a team from the United States.

Researchers at the Fred Hutchinson Cancer Center in Seattle announce good results in first tests of laboratory in what is already accepted as a new concept in immunization against this pathogenic agent.

Dr. Andrew McGuire and his team explain in an experimental study, which appears in Cell Reports Medicine, how they work with a vaccine of nanoparticles that mimic those found on the surface of this virus.

The surface proteins gH and gL work like little levers, allowing the live virus to pass through the outer membranes of the cells it infects. And this has been, precisely, the objective of the research of Dr. McGuire, a molecular biologist specializing in the design of vaccines against the human immunodeficiency virus (HIV), which causes AIDS.

They are research focuses on the development of immunogens, molecules that would cause the immune system to generate protective proteins or neutralizing antibodies to block the virus.

Because HIV mutates so rapidly, conventional antibodies do not offer long-lasting protection. Its goal is to persuade the immune system to generate broadly neutralizing antibodies, which are difficult for HIV to evade and more effective at protecting against different strains.

Epstein-Barr virus vaccine

In 2018, this researcher highlighted these two proteins by showing that if they were blocked they could prevent the Epstein-Barr virus from infecting two types of human cells: the epithelial cells that line the mouth, nose and throat; and blood B cells that produce antibodies. Since then, they have been working on the vaccine.

The idea of ​​this preparation is to train the immune system to recognize fictitious copies of the gH/gL proteinsso that if the organism finds the same forms on the surface of the virus, it generates antibodies against them.

The action is similar to how vaccines work against SARS-CoV-2, which causes Covid-19: training the immune system to attack the distinctive spikes on the surface of the new coronavirus, by causing the body to manufacture fictitious copies of that spike. .

McGuire’s experimental EBV vaccine has been designed to show its dummy proteins attached to nanoparticles, either parked one protein per particle or displayed in multi-copy arrays. These dummy screens stimulate the production of antibodies that can bind to the real gH/gL proteins on the viral surface.

As they point out in their study, swarms of these antibodies would disrupt the Epstein-Barr virus’s ability to use these lever proteins to convert healthy cells into muscle. The ideal scenario is that the immune system could invoke these same antibodies repeatedly.

So far McGuire and his team, which includes study first author Harman Malhi, have tested five different versions of their vaccine on laboratory mice. Each version differed by the number of gH/gL protein copies carried and displayed by the nanoparticles: one, four, seven, 24 or 60.

digital ‘scaffolding’

According to McGuire, all the multiple-copied nanoparticles worked well, but the best results came from two of them, those with four copies and those with 60 copies. They then analyzed serum from rodents given the 60-copy version. and tested its protective capabilities in another group of mice infected with a lethal dose of the virus.

Los results they were spectacular: 100% of the mice that received antibodies generated from the 60-copy vaccine survived; while 75% of those who received antibodies generated from the single-copy vaccine died, as did all of those who received a placebo.

These two better-performing versions differed from the others in that their nanoparticle scaffold used to carry and display the multiple dummy proteins was computer-designed.

These scaffolds, like most of the biological materials, are also protein structures, but the computer versions are artificial constructs designed for efficiency. In these experiments, the artificial protein carriers appeared to have outperformed their natural counterparts.

The four-copy scaffold was developed by computational biologist Dr. Phil Bradley of Fred Hutch and his team, while the 60-copy version was developed by Dr. Neil King of the Institute for Protein Design at the University of Washington. Washington.

Now, McGuire’s group is conducting additional preclinical trials to see if this trial’s approach remains promising and safe enough to test in humans.

This work was funded by the US National Institutes of Health; the Bill and Melinda Gates Foundation; Audacious and Violet Project; the Washington Research Foundation and by the Burroughs Wellcome Fund.

The Epstein-Barr virus

The Epstein-Barr virus was the first virus shown to cause cancer in humans. Its discovery in 1964 led to a growing recognition that viruses and other pathogens are associated, directly or indirectly, with up to 20% of all cancers worldwide.

Removing that burden is the goal of the newly formed Fred Hutch Pathogen-Associated Malignancies Integrated Research Center, which is led by Galloway and brings together infectious disease researchers like McGuire and experts in cancer biology, global oncology, immunotherapy and other specialties to better understand, treat and prevent cancers related to infectious agents.

British researcher Anthony Epstein first identified the virus that bears his name in tumor samples sent to him by Denis Burkitt, an Irish surgeon and missionary working in Uganda in the 1950s.

The samples were from a rapidly lethal cancer of the immune system first described by Burkitt in 1958. Today, Burkitt’s lymphoma remains the most common cause of death from childhood cancer in sub-Saharan Africa.