Newly Characterized Measles-Neutralizing Antibodies Show Treatment Potential

Scientists at La Jolla Institute for Immunology have characterized human antibodies capable of neutralizing measles virus. These antibodies attach to key sites—the fusion protein and attachment protein H—preventing the virus from entering host cells. In a rodent model of measles infection, infusions of these antibodies lowered viral load 500-fold.

The antibodies serve dual roles in protection and therapy. "These antibodies work as prophylaxis—to protect from initial infection—and they work after viral exposure as a treatment to fight measles infection," says Erica Ollmann Saphire, who led the Cell Host & Microbe study. "It may be possible to give someone an infusion of these antibodies and deliver the immune response they wish they had."

Decreased vaccination rates have sparked deadly measles outbreaks across the United States and globally. The measles vaccine proves safe and effective but relies on live, weakened virus, barring its use in immunocompromised individuals, pregnant people, chemotherapy patients (including children), infants under 12 months, and children until fully vaccinated at age 6. "There are a growing number of people that can't be vaccinated or haven't been fully vaccinated," Saphire notes. "The very same people who can't be vaccinated or can’t be vaccinated yet, are the same people for whom a measles virus infection would be the most severe—or be lethal."

No measles-specific treatments exist today. Monoclonal antibody therapies, delivering numerous copies of a single neutralizing antibody, already prevent RSV in infants annually.

To design a monoclonal antibody treatment for measles, researchers need a clear picture of how human antibodies fight the virus. Saphire and her colleagues began by harnessing cryo-EM to capture the first-ever glimpses of how antibodies bind to the measles virus. They started by examining mouse antibodies, and they published that work in a recent Nature Communications paper. That initial study showed where measles virus is vulnerable to antibody attack. The mouse antibodies latched onto one key part of the measles virus, called the fusion protein, to block the virus from entering a host cell.

Could human antibodies do the same thing? To find out, the researchers analyzed blood from a clinical research volunteer. This volunteer had been vaccinated against measles many years before, so they already had antibodies ready to fight measles virus.

The next step was to test these antibodies in a preclinical animal model. Collaborators at The Ohio State University tested four lead antibodies in cotton rats. All reduced viral loads when administered before exposure or 24-48 hours post-infection. Antibody 3A12 eliminated detectable circulating virus.

These structural data and antibodies offer a foundation for pre- or post-exposure measles therapies. "Now we know what we're aiming for, and we have the antibodies we need," Saphire states.