Mechanism(s) of long-term humoral immunity and immune suppression induced by wildtype Measles virus in rhesus macaques

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Abstract Measles virus (MeV) causes a highly contagious systemic viral infection that remains an important cause of morbidity and mortality in children worldwide. While recovery from measles infection induces life-long protective immunity, it also causes immune amnesia which can lead to higher susceptibility to other infections. To better understand the long-term immune responses induced by the MeV vaccine versus wildtype (WT) MeV, first, we studied rhesus macaques for six months after WT MeV or Measles-Mumps-Rubella (MMR) inoculation. We quantified total antibody secreting cells (ASC) and MeV-specific ASCs in peripheral blood mononuclear cells (PBMCs) using well-characterized in house methods for ELISpot; and assessed MeV-specific IgG, avidity, and plaque reduction neutralization titers. Second, we assessed whether the loss in immune memory post WT MeV infection is linked to eviction of B cells from the bone marrow (BM) into circulation. BM and PBMCs from live attenuated MeV (LAMV) vaccinated monkeys were cultured and supernatant were assessed for isotype and antigen specificity by ELISA. PBMC cultures produced detectable amount of MeV-specific antibody and antibody recognition profiles will be compared via Virscan, a phage-display technology for epitope mapping. A novel panel of non-human primate (NHP) pathogen peptides representing Herpesviruses, Retroviruses, Adenoviruses, Pneumoviruses, and Enteroviruses were developed and expressed using the system with plans to use them to characterize changes in antibody production. We hypothesis that the robust immune response to WT MeV is accompanied by eviction of long-lived plasma cells from BM niches resulting in a loss of Ab diversity that does not occur after infection with LAMV. Supported by grants from NIH (5R01AI153140-03)