Felix Nettersheim, M.D.

What if we can enhance a heart disease vaccine by blocking regulatory molecules?

Funded: January 2023
Funded By: The generosity of LJI Board Director (’16-’22) Tom Tullie and the Tullie Family

Worldwide, almost 18 million people die each year from cardiovascular diseases. A major cause of heart disease is an uncontrolled autoimmune attack against the blood vessels. Accumulating evidence suggests that a vaccine with cholesterol particles can dampen this autoimmune process. However, such vaccines elicit a considerably weaker response compared to vaccines against bacteria or viruses. I aim to investigate whether blocking two regulatory molecules can increase the effectiveness of a heart disease vaccine.

My first experiment was to analyze the vaccine response in mice lacking one of the two regulatory molecules. While a lack of the first molecule did not make a difference, the vaccine response in mice lacking the second molecule was more than doubled compared to control mice.

Next, I tested whether pharmacological blockade of both molecules simultaneously enhances the vaccine response. Consistent with the first experiment, blocking one molecule approximately doubled the number of responding cells, whereas blocking the other had no relevant effect. Strikingly, blocking both molecules together enabled a more than six-fold higher vaccine response compared to control mice.

My third experiment, which I have yet to perform, will provide evidence as to whether the blocking strategy can enhance the clinical efficacy of a heart disease vaccine.

SPARKing Impact: I intend to test a novel strategy to enhance the efficacy of such a vaccine for cardiovascular disease. This work could eventually help bring this promising approach from bench to bedside.