Mumps resurgence despite MMR: Limitations of current vaccines and the need for new strategies.

Mumps has reemerged globally despite widespread use of the measles - mumps - rubella (MMR) vaccine, contrasting with the successful control of measles and rubella. This divergence reflects important limitations in the performance of the mumps component of the MMR vaccine and the programmatic framework in which it is delivered. Evidence from multiple settings indicates that mumps outbreaks continue to occur in highly vaccinated populations, driven by waning immunity, non-sterilizing immune responses, and sustained transmission in high-contact environments. In parallel, many low- and middle-income countries do not include mumps vaccination in national immunization programs, resulting in large susceptible populations and under-recognition of disease burden. Immunologically, current vaccines induce less durable humoral immunity, limited mucosal protection, and poorly defined correlates of protection, while antigenic differences between vaccine and circulating strains may further reduce effectiveness. Programmatically, the fixed MMR platform limits flexibility in tailoring strategies specific to mumps epidemiology. Addressing these challenges will require rethinking current approaches, including targeted booster strategies, consideration of stand-alone or bivalent vaccines, and development of next-generation vaccines capable of inducing broader and more durable, potentially mucosal immunity. A shift toward mumps-specific vaccination strategies is essential for sustained control.