Innate and adaptive immune responses to measles virus and measles vaccine.

摘要

Wild-type (WT) measles virus (MeV) can induce immune suppression against secondary pathogens in the host while the live-attenuated vaccine strain does not. This immune suppression is the reason that measles is still one of the major causes of deaths worldwide. In order to understand the mechanism of immune suppression, the innate and adaptive immune responses after MeV infection needs to be better characterized. The innate immune response to viral infection frequently includes induction of type I interferons (IFN), but many viruses have evolved ways to block this response and increase virulence. Previous in vitro studies of IFN production after infection of susceptible cells with measles virus (MeV) have often reported greater IFN synthesis after infection with vaccine than wild type strains of MeV. However, the possible presence in laboratory virus stocks of 5' copy-back defective interfering (DI) RNAs that induce IFN independent of the standard virus has frequently confounded interpretation of data from these studies. In vivo studies have not detected IFN after infection with vaccine or WT strains of MeV. To further investigate MeV strain-dependent differences in IFN induction, human monocyte derived dendritic cells (moDCs) and rhesus macaques were infected with the WT Bilthoven strain and the vaccine Edmonston-Zagreb strain of MeV. Presence of DI RNAs in vaccine stocks resulted in greater maturation of moDCs, inhibition of virus replication and induction of higher levels of IFN and ISGs. In the absence of DI RNA, levels of type I IFN, type III IFN and ISG mRNAs were similar between wild-type and vaccine strains when compared at the same levels of infection. The adaptive immune responses after primary and secondary infection with WT and vaccine strain of MeV have been studied before. We assessed the adaptive immune responses in different contexts such as after a third dose of measles vaccine in young human adults and after delivery of measles vaccine sublingually to rhesus macaques. There was no increase in human T-cell responses after a third dose of measles vaccine at one month and one year post-vaccination. There was also no increase in antibody and T-cell responses observed after sublingual measles vaccination in rhesus macaques. However, the monkeys were partially protected from WT MeV challenge as assessed by infection levels and adaptive immune responses. As measles control will be accelerated in the future and eradication efforts will progress, these findings will be relevant as immune suppression, waning immunity and alternative vaccine delivery methods will be important factors to consider.