Mechanistic insights into immune amnesia and immunity induced by measles infection and vaccination via comprehensive antiviral antibodies profiling

Abstract

Abstract Measles is a disease known to induce acute immune amnesia and immunosuppression with increased susceptibility to other infections, while paradoxically conferring patients with life-long immunity to measles. However, it is not clear if the live-attenuated measles vaccine (LAMV) induces immunosuppression comparable to the wild-type measles (WT MeV) infection, nor how mechanistically LAMV and WT MeV affect antibodies specific to different pathogens. Therefore, we utilized VirScan, a phage-display immunoprecipitation and sequencing (PhIP-seq) technology for virome-wide detection of antibodies against viral epitopes, to compare longitudinal antibody diversity in plasma samples from WT MeV and LAMV-infected rhesus macaques (RMs) (n=10 and 6 respectively, with 5 longitudinal timepoints at D0, D14/15, D28, D84/89, D112/168/176). Preliminary analysis showed that WT MeV led to more long-term depletion of pre-existing antibodies to various viral peptides, while mounting a MeV-specific antibody response with greater intensity and breadth than LAMV-infected RM. Furthermore, in our sex difference analysis, male RMs elicited a stronger MeV response than female, particularly to N protein; also a more polyclonal MeV humoral response In summary, our work provided crucial mechanistic insights into immune amnesia and immunity induced by natural infection versus vaccination, highlighting the public health value of the measles vaccine in averting MeV-induced immune amnesia.