Potent Human Antibodies Neutralize Measles Virus

The measles virus is a highly contagious disease that results in fever, cough, and a blotchy rash. The approval of the measles, mumps, and rubella (MMR) vaccine in the 1960s significantly slashed disease rates; in fact, it was declared eliminated in the United States in 2000. However, in more recent years, a drop in vaccination rates has led to a rise in measles outbreaks across the United States and around the world.

"There are a growing number of people that can't be vaccinated or haven't been fully vaccinated," said Erica Ollmann Saphire, a structural biologist and immunologist at the La Jolla Institute for Immunology in a press release. "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." This motivated her and her colleagues to map the epitopes, which are specific parts of a virus recognized by antibodies elicited by the vaccine, and identify a measles-specific therapy for this vulnerable patient population.

In a new study, published in Cell Host & Microbe, Saphire and her colleagues identified a panel of human antibodies that target measles virus from MMR-vaccinated patients.¹ These antibodies bound to either the measles fusion protein (F) or the attachment protein (H) on the virus’s surface and blocked infection in an animal model. Because the team observed both prophylactic and therapeutic protection with these antibodies, the work may guide the development of future treatments.

Most vaccine-elicited antibodies bind to the H protein; however, a percentage of antibodies against the F protein are also potent viral inhibitors, though their interactions are not fully characterized. In a previous study, Saphire and her colleagues used cryo-electron microscopy on chimeric mouse-human antibodies that target the F protein.²

With this method, they observed a clearer picture of how these antibodies bind to the measles virus. When the virus interacts with a human cell, it undergoes a shape change to fuse itself [to the host cell membrane and subsequently infect the host cell. Notably, four mouse antibodies targeted distinct F conformations: three of these antibodies bound to prefusion epitopes, preventing the shape change and in turn blocking the virus from entering the cell.

In this new study, the team sought to identify if a similar pattern was present in human antibodies. They analyzed blood from a previously vaccinated patient and isolated a panel consisting of 52 anti-H and 46 anti-F antibodies. Then, the researchers used 3D imaging techniques to map the structural epitopes on these viral proteins and their interactions with the human antibodies: They recognized four major sites on the H protein and five on the F protein. Just as they observed in their previous work, these antibodies also had neutralizing potential.

"We found that these antibodies are exceptionally potent," said study coauthor Dawid Zyla, who is a postdoctoral researcher in Saphire’s group, in a statement. "Two orders of magnitude better than comparable molecules reported at conferences."

When they tested these antibodies in a preclinical rat model, they found that if they gave the antibody panel before measles exposure or within 24 to 48 hours after infection, the antibodies reduced the viral load—up to 500-fold. These protective antibodies targeted distinct, non-competing epitopes, suggesting that they can be used as a powerful treatment for patients.

While further work is needed to bring these insights to the clinic, the researchers are optimistic in these findings providing new avenues for prophylactic or therapeutic intervention against measles.