Insights into pathologic mechanisms occurring during serious adverse events following live zoster vaccination

Abstract

An effective live zoster vaccine has been widely used around the world. Although no deaths occurred in the original large clinical trial, we analyzed 10 serious adverse events, including six deaths that have subsequently occurred in four countries. The goal is to define the viral pathogenesis of these unexpected adverse events secondary to a viremia with dissemination of the vaccine virus. We also propose a new hypothesis for acute retinal necrosis that occurs post-immunization.

Keywords: VZV ORF0; acute retinal necrosis; pathogenesis; single nucleotide polymorphisms; varicella vaccine; varicella-zoster virus.

Fig 1

Schema for pathogenesis of acute retinal necrosis following live zoster virus vaccination. All neuronal pathways are described in cited articles in the text. ICA, internal carotid artery; OA, ophthalmic artery; CRA, central retinal artery.

Fig 2

Diagram of VZV ORF0 in four varicella strains. ORF0 is the initial ORF in the unique long region of the wild-type varicella genome. The ORF0 product is a glycosylated type 2 transmembrane protein; it is the homolog of herpes simplex virus UL56. The stop codon is mutated in the vaccine strain. Wild type; Zoster, child with zoster caused by a variant vaccine genotype with wild-type ORF0 sequence. Vaccine type; Ellen, laboratory VZV strain characterized as having a vaccine-type ORF0 sequence. GenBank: wild type, AB097933; vaccine type, AB097932; VZV Ellen, JQ972913.