While an attenuated vaccine against mumps has played a role in controlling the epidemic of this disease worldwide, some problems with efficacy and safety of the vaccine are still present. In the work described here, a novel mumps vaccine with good immunity and safety was developed by selecting an antigen component of the mumps virus. The results suggest that this purified antigen vaccine is immunogenic in animals and is capable of inducing a specific neutralizing antibody response against viral HN, but not against other viral proteins. The clinical and pathological observations after challenge of vaccinated rhesus monkeys indicated further that the immune response induced by this vaccine provided complete protection from wild-type virus infection. Furthermore, the immunological analysis and clinical observation of experimental monkeys that were immunized with the vaccine, followed by infection with wild-type virus, suggest that no abnormal changes in expression of inflammatory cytokines and no clinical allergic reaction were found at 1 month after challenge.