“As mumps makes a global resurgence, my SPARK project aims to design a safer and more effective protein-based vaccine to address the limitations of the current MMR vaccine.”
Can we design a better mumps vaccine that offers potent lifelong immunity?
Mumps has re-emerged as a persistent public health threat due to incomplete vaccination coverage, waning immunity, and the increasing number of immunocompromised individuals who cannot be vaccinated. Mumps is characterized by swelling of the salivary glands, fever, headaches, and muscle pain. In severe cases, it can cause serious complications such as encephalitis, neurological damage, deafness, heart and kidney infections, and testicular atrophy in males. My project aims to address this resurgence by exploring new strategies to strengthen immunity and enhance vaccine effectiveness to protect vulnerable populations.
The mumps virus fusion protein enables the virus to merge with human cells. This protein also presents a promising target for developing a next-generation vaccine. The fusion protein is critical for immune recognition and could be the foundation for a safer recombinant subunit vaccine. However, scientists have no structural model of the mumps virus fusion protein, leaving a significant gap in our understanding of how to stabilize it effectively. We know that the fusion protein transitions from a pre- to post-fusion state during viral entry, but the wild-type version—used in both the MMR vaccine and previous recombinant attempts—is unstable and rapidly adopts the post-fusion conformation, which is ineffective for vaccination.
With SPARK support, I aim to bridge this gap by utilizing LJI’s cryo-EM facility to engineer stabilizing substitutions in the mumps fusion protein, keeping it locked in its pre-fusion state. This approach will enable the development of a safer, more effective, and longer-lasting vaccine that can induce a stronger and more durable immune response. Importantly, a stabilized protein-based vaccine would also provide a critical alternative for pregnant people, infants, and immunocompromised individuals who cannot receive the live MMR vaccine and are at increasing risk of infection.