Immunogenicity and efficacy of two candidate human metapneumovirus vaccines in cynomolgus macaques

Human metapneumovirus (HMPV) is an important cause of acute respiratory tract disease for which the development of vaccine candidates is warranted. We have previously described the generation of an iscom matrix-adjuvanted HMPV fusion protein subunit vaccine (Fsol) and a live-attenuated vaccine (HMPVM11). Here, we evaluate the immunogenicity and efficacy of these vaccines in cynomolgus macaques. Immunization with Fsol induced HMPV F-specific antibody responses, virus neutralizing antibody titers, and cellular immune responses, but the induced humoral immune response waned rapidly over time. HMPVM11 was strongly attenuated and displayed limited immunogenicity, although immunization with this virus primed for a good secondary HMPV-specific lymphoproliferative response after challenge infection. The duration of virus shedding in HMPVM11-immunized animals was reduced compared to sham-immunized animals. Both vaccines induced HMPV-specific immune responses, but the rapid waning of immunity is a challenging obstacle for vaccine development.