Scientists at Harvard Medical School have discovered that antibodies made in response to a vaccine for one hemorrhagic fever virus — Junin — can also disarm another virus, Machupo.
This breakthrough is significant because it sets the stage for the design of vaccines that can work against multiple or all members of a viral family, despite differences in molecular makeup.
Junin and Machupo are both known as hemorrhagic fever viruses, which can induce massive, and at times fatal, internal bleeding. Another such virus is Ebola, which devastated West Africa with an outbreak in 2014-2016. The lack of preventive therapies for these types of infections has long frustrated public health officials’ efforts to avert outbreaks.
The findings by the team from Harvard, published in the May 14 issue of Nature Communications, shows that people and primates vaccinated against Junin appear to be more resilient to Machupo as well. This marks the first molecular proof of this capability.
“Our findings raise the tantalizing possibility of designing universal therapies using antibodies made to one virus for which there is a vaccine as a way to prevent or treat other viruses for which there are none,” said senior author Jonathan Abraham, assistant professor of microbiology and immunobiology at Harvard Medical School and an infectious disease specialist at Brigham and Women’s Hospital. “We believe our results are a step in that direction.”
Junin and Machupo are in what is called the Arenaviridae family of hemorrhagic fever viruses, which is composed of more than 30 viruses. Typically, between 15 and 30 percent of people infected with one these viruses die. These viruses are specific to South America.
A Junin vaccine established in the 1980s has immunized about 95 percent of people who get it. As a result of the vaccine, cases of Junin in Argentina went from about 2,000 per year to about 50 per year. However, there is no specific vaccine for Machupo, but outbreaks have been relatively small and contained.
To develop a vaccine that acts against multiple or all viruses of the same family, like Junin and Machupo, scientists have focused on a commonality across related viruses – a “molecular key” called a protein receptor binding site (RBS). The RBS fits into surface proteins on the host cell like a key in a lock. Thus, researchers have worked to develop treatments that mimic the “lock” of the host cells to fool the virus into thinking it’s attached to a host cell. In fact, it is locked into an antibody that renders it incapable of entering and infecting host cells.
“Even among viruses that are related and share similarities in the molecular makeup of their receptor bindings sites, you still end up with a substantial degree of variability,” Abraham said. This variability has historically thwarted efforts to design protective antibodies toward one hemorrhagic fever virus as a way to disarm others.
However, the Harvard researchers identified a small portion in the molecular keys used by Junin and Machupo that is identical and responds to the same antibodies. Thus, both viruses sensitive to the same vaccine. The findings suggest that such common areas may exist among other members of the Arenavirus family.
“This approach can play an important role in controlling human infection and its most devastating consequences — a goal that’s remained elusive,” Abraham said. “As we get better in our ability to home in on progressively tinier parts shared across all viruses, we can start eyeing new precision-targeted therapies designed to work on conserved areas across multiple viral species.”