How Does a Wild-Type Measles Virus Behave Differently From a Live-Attenuated Virus?

The differences do not mean that the measles vaccine is ineffective.

Scientists have uncovered new information that helps explain why measles immunity conferred via natural infection is stronger than that conferred by the attenuated virus in the measles vaccine.

Wild-type measles virus and live-attenuated measles virus are antigenically similar, but in a new paper in Science Translational Medicine, corresponding author Diane E. Griffin, MD, PhD, of the Johns Hopkins Bloomberg School of Public Health, and colleagues, offer new insights about how the 2 types of virus behave differently and how that translates into different levels of protection.

The team studied both types of the virus, wild-type (WT) and live-attenuated (LAMV) in rhesus macaques. What they found was that the WT virus was much more efficient and thorough in its spread. It efficiently replicated in both B and T lymphocytes, and the viral RNA could still be detected after 10 weeks.

Conversely, LAMV replicated efficiently in the respiratory tract, but had limited ability to spread in the lymphoid tissue or peripheral blood mononuclear cells, Griffin and colleagues wrote. Moreover, the RNA of LAMV was undetectable in most animals after just 24 days.

Griffin told Contagion® she was surprised by the specific differences, such as the ways the viruses interact differently with lymphocytes.

“I was surprised to learn that the vaccine virus differs from the WT virus specifically in its ability to replicate in lymphocytes and that this difference is not in ability to infect lymphocytes, but rather than to produce virus after infection,” she said. “This is a clue that we are currently pursuing to understand mechanisms.”

While the study exposes differences in how the measles virus acts when attenuated, Griffin noted that the differences don’t mean the vaccine is ineffective. Indeed, while some patients today are old enough to have survived the measles and therefore won lifetime immunity, other patients who walk into a physician’s office might have only had one dose of the vaccine, instead of the now-recommended 2 doses. Those patients are protected, too, she said.

“The vaccine elicits similar immunity (very protective), but it is not as durable,” she said.

“However, even if vaccinated people become infected, they develop much milder disease, so are partially protected because they have some memory response that are quickly reactivated.”

Griffin said the main import of the booster shot is to protect the roughly 5-15% of people who don’t respond to the first dose, a number that varies depending on the patient’s age at the first vaccination.

However, the study sheds light that could be important in terms of helping to develop stronger vaccines in the future. For instance, it raises the question of whether different delivery methods or stronger doses might make immunity more durable.

“These studies compared natural (wild type) measles with vaccine and provided the clue that replication in lymphoid tissue was an important difference,” she said. “We might be able to figure out how there can be more long term stimulation of immune responses in lymphoid tissue as a general approach to improving the durability of vaccine responses."