Characterization of varicella zoster virus-specific monoclonal antibodies

Abstract

Abstract Herpes zoster (HZ or shingles) is the clinical manifestation of varicella zoster virus (VZV) reactivation. HZ typically develops as people age due to decreased cell mediated immunity. However, the relative importance of humoral immunity against VZV remains somewhat controversial. The goal of this study was to examine the breadth and functionality of VZV-specific antibodies. Direct enumeration of VZV-specific antibody secreting cells (ASC) via ELISPOT showed that Zostavax® vaccination can induce both IgG and IgA ASCs seven days after vaccination, but not IgM ASCs (IgG>IgA≠IgM). The frequency of VZV-specific ASCs was from 33–55% of the total IgG ASCs. ASCs were also single-cell sorted from five subjects (> 60 years old) and 25 VZV-specific monoclonal antibodies (mAbs) were successfully cloned and characterized. These mAbs had on average ~ 20 somatic hypermutations per VH gene, similar to the number of mutations seen in mAbs characterized after seasonal influenza vaccination (Li GM, PNAS, 2012). Fifteen of the 25 mAbs were gE-specific, whereas the remaining mAbs were gB, gH or gI-specific. The antibodies were then tested for in vitro neutralization and inhibition of cell-to-cell spread, which will be discussed. These data indicate that Zostavax® vaccination can induce a memory B cell recall response and gE is the predominant antibody target. However, the relative importance of these antibodies for protective immunity against VZV reactivation will be discussed.