Scientists identify powerful human antibodies capable of neutralizing measles virus

Scientists at La Jolla Institute for Immunology (LJI) are the first in the world to characterize human antibodies capable of neutralizing measles virus. These antibodies bind to key sites on measles virus and prevent the virus from entering host cells.

The new panel of human antibodies may form the basis for future medical therapies against measles infection. In the study, an infusion of these antibodies resulted in a 500-fold lower viral load in a rodent model of measles infection.

"These antibodies work as prophylaxis-to protect from initial infection-and they work after viral exposure as a treatment to fight measles infection, " says LJI Professor, President & CEO Erica Ollmann Saphire, Ph.D., who led the new 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."

The urgent need for measles therapies

Until recently, enough people were vaccinated against measles virus that the risk of exposure for this unvaccinated group was very low. Unfortunately, that community protection, called "herd immunity," is no longer.

Right now, there are no measles-specific therapies to help patients. The new study shows that monoclonal antibody therapies may be the way forward.

LJI scientists identify powerful antibodies

Monoclonal antibody therapies work because they contain many copies of a neutralizing antibody. These therapies are widely used for a variety of infectious diseases. Even infants receive monoclonal antibody therapies each year to prevent respiratory syncytial virus (RSV).

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 an imaging technique called cryo-electron microscopy (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-in stunning detail-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.

"We found that these antibodies are exceptionally potent," says LJI Instructor Dawid Zyla, Ph.D., who served as study co-first author. "Two orders of magnitude better than comparable molecules reported at conferences."

Measles virus is a shape-shifting virus. When it meets a human cell, it unfolds to reveal viral machinery that fuses with the host cell membrane. The new study shows that antibodies targeting the fusion protein work by locking the protein in place, leaving the virus unable to shape shift and infect a host cell.

Moving forward with preclinical research

The next step was to test these antibodies in a preclinical animal model.

Study collaborators at The Ohio State University carried out key experiments using cotton rats as a model. They found that all four lead antibodies reduced the viral load when given either before measles exposure or within 24 to 48 hours after infection. One, an antibody called 3A12, which binds to a site on the F protein, rendered the circulating virus actually undetectable.

While more work needs to be done, the researchers see these antibodies as promising tools in the fight against measles. Their new images of the antibody structures provide the materials needed to make the world's first before- or after exposure treatment for measles virus.

Source:

La Jolla Institute for Immunology

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