If there’s one take-home message for the general public about the coronavirus vaccines approved in the U.S., it’s that they are remarkably effective.

But Michigan State University’s Morteza Mahmoudi is raising awareness about an important subtlety: The vaccines developed by Moderna and Pfizer-BioNTech appear to work slightly better for males than for females.

Both vaccines use tiny orbs, or nanoparticles, to deliver their active ingredients to cells in our immune systems. For years, Mahmoudi has been studying how and why nanomedicines — therapies that use nanoparticles — can affect patients differently based on their sex and he believes this could be a factor with the vaccines.

The Johnson & Johnson vaccine has also drawn attention to sex differences because its rare blood-clotting side effect has affected predominantly female recipients. The J&J vaccine, however, uses modified adenoviruses rather than nanoparticles to help teach our immune systems to fight off the coronavirus. That said, Mahmoudi has shown in earlier work that viruses can transfect the cells of males and females differently.

Now, he’s focusing on the nanomedicine component. He’s published three peer-reviewed papers calling attention to the role of sex in nanomedicine studies, both in general and as they relate to coronavirus vaccines.

“We need to monitor these sex differences and report them to the scientific community and the public,” said Mahmoudi, an assistant professor in the Department of Radiology and the Precision Health Program. “It can be very helpful in developing future strategies and as we prepare for future threats.”

To develop those future strategies, researchers must better understand what causes patients of different sexes to respond differently to nanomedicines, Mahmoudi said. To that end, Mahmoudi is advocating for systemic changes in how nanoparticles are used and studied in medicine with an article published May 20 in the journal Nature Communications.

In the article, he outlines four large challenges in researching the role of sex in nanomedicine performance along with strategies to mitigate them moving forward.