As measles roars back, scientists find antibodies that could offer protection

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Using the blood of a 56-year-old woman vaccinated against measles, scientists have isolated a fighting force of four potent virus-blocking antibodies that could pave the way toward a treatment for people exposed to the highly contagious respiratory disease making a comeback in the United States.

A safe, highly effective vaccine for measles has been available since the 1960s, and the U.S. officially eliminated the disease in 2000, with sporadic cases and outbreaks. But dropping vaccination rates have sparked large outbreaks in multiple states, and the country is edging closer to the virus spreading freely again-which puts more people at risk.

New ways to block or treat measles would be particularly important for people who are immunocompromised and babies under the age of 1, because they are not eligible for the vaccine, leaving them unprotected amid a growing number of cases.

“Measles was a problem that was solved. Until it wasn’t solved anymore,” said Erica Ollmann Saphire, president of the La Jolla Institute for Immunology who led the study published Thursday in the journal Cell Host & Microbe. But she and other scientists stressed that this approach was not a substitute for a vaccine.

“The treatment is always going to be more expensive than the vaccine. It’s the best bang for your public-health buck - this is for people that couldn’t be vaccinated,” Saphire said.

The new work is a basic science study. In rodents, the experimental antibodies knocked down the amount of virus in their lungs when given one to two days after infection. If further testing and refinement show the approach is safe and effective in people, it could be used after exposure - analogous to giving antivenom after someone has been bitten by a venomous snake, Saphire said, or as a preventive therapy similar to the RSV antibody used to protect babies.

A ‘solved’ virus that still holds mysteries

Today, when scientists want to create countermeasures against a new virus, they deploy an arsenal of sophisticated tools to decode the 3D shape of the proteins that viruses carry on their surface. Those surface proteins can act like homing devices and molecular crowbars that allow viruses to break into cells.

Scientists also study the structure of antibodies generated by the immune system to block those viral proteins, to help them design vaccines or lab-generated antibody drugs called monoclonal antibodies.

Saphire had focused on using these tools against emerging threats such as Ebola and Lassa fever, but she also became fascinated by what scientists still did not know about measles. For decades, scientists had no need to do this basic science. The measles vaccine is a live, weakened strain of the virus that is remarkably effective at teaching people’s immune systems how to defend against a real infection.

Saphire and colleagues searched in the blood of a vaccinated person and found dozens of antibodies that stuck to two different proteins crucial for measles infection - the H protein that allows the virus to latch on to cells, and the F protein that helps it fuse to cells.

The F protein is a spring-loaded molecule that morphs its shape once it receives a signal from the H protein to help the virus invade a cell. They selected four extremely potent candidates that target both proteins - two that lock the F into one shape, and two others that bind to the H protein to block its ability to latch on to cells.

Roberto Cattaneo, a biochemist who has studied measles virus for 40 years and was not involved in the new study, said that a detailed understanding of the virus has been lacking in part because of the existence of a highly effective vaccine.

“It’s wonderful to know how it works. It may be relevant for emerging viruses. I find it very interesting because I’ve worked on measles for decades now, and this is all quite impressive - the detail in which we can now sort out how the entry of the virus [into cells] works,” Cattaneo said.

But because the measles virus makes copies of itself inside lymph nodes and transmits from cell-to-cell, he said there could be challenges in finding ways to deliver a lab-generated antibody so that it blocks infection.

Prevention remains easier and more effective

With a vaccine and herd immunity protecting those who could not get the shot, there was for years no need to develop a lab-generated antibody drug.

Paul Offit, a pediatrician and director of the Vaccine Education Center at Children’s Hospital of Philadelphia, said that this approach would probably have to be given shortly after exposure to be effective, long before a person develops symptoms.

He added that it’s already possible to give people immune globulin, a treatment of concentrated antibodies created from people who have immunity.

“We solved the problem. We have a measles vaccine, and even though we have the most contagious infection on Earth, we were able to eliminate it from the U.S.,” Offit said. “It’s hard to treat … by the time you develop symptoms, which is why prevention is the better idea.”

And unlike the multipronged immune defenses generated by vaccines, antibody drugs or a cocktail of them only block viruses in one or, at most, a handful of ways.

David Kennedy, an associate professor of biology at Pennsylvania State University who studies the evolution of infectious diseases, raised the concern that this could cause the virus to change in a way that made vaccines less effective.

“They’re characterizing the way that antibodies attack the measles virus, and I think that doing that is great,” Kennedy said. “It’s creating this information where we can understand: How complex is our immune response against measles? How possible is it that a monoclonal will drive evolution in a dangerous direction?”

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