Improved level and longevity of protective immune responses in measles virus with efficient replication in blood and lymphoid tissue

Abstract

Abstract Infection with wild type measles virus (wt-MV) is an important cause of childhood mortality and is also known to induce remarkable life-long protective immunity. Despite the antigenic similarities between wt-MV and live-attenuated measles virus vaccine (LAMV), the protective immunity after measles vaccination is not as robust or long-lived. To identify mechanisms that contribute to the longevity of immune responses induced by wt-MeV infection, we compared parameters of virologic and immunologic responses after respiratory infection with wt-MeV and LAMV in rhesus macaques. Analysis of viral RNA in various tissues revealed distinct in vivo tropisms between the two strains of virus. Wt-MeV caused efficient hematogenous spread and prolonged presence of viral RNA, while LAMV caused transient localized infection in the respiratory tract. Plasma levels of cytokines IL-1β, IL-12 and interferon (IFN)-γ and chemokines CCL2, CCL11, CXCL9 and CXCL11 were increased after wt-MeV, but not LAMV infection. Infection with wt-MeV or LAMV induced comparable levels of viral-specific T cells, but significantly higher levels of protective antibody and more long-lived plasma cells were observed after wt-MeV infection. Therefore, distinct patterns of in vivo virus replication, efficiency of hematogenous spread and persistence of viral RNA are associated with the altered virulence and the level and longevity of the humoral response. Our results establish a link between life-long protective immunity and the ability of wt-MeV to spread efficiently in lymphocytes and to be cleared slowly.