The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

NCT00534248.

Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory neurons after primary infection (chickenpox) and subsequently may reactivate to cause zoster. The mechanism by which this virus maintains latency, and the factors involved, are poorly understood. Here we demonstrate, by immunohistochemical analysis of ganglia obtained at autopsy from seropositive patients without clinical symptoms of VZV infection that viral regulatory proteins are present in latently infected neurons. These proteins, which localize to the nucleus of cells during lytic infection, predominantly are detected in the cytoplasm of latently infected neurons. The restriction of regulatory proteins from the nucleus of latently infected neurons might interrupt the cascade of virus gene expression that leads to a productive infection. Our findings raise the possibility that VZV has developed a novel mechanism for maintenance of latency that contrasts with the transcriptional repression that is associated with latency of herpes simplex virus, the prototypic alpha herpesvirus.Latency has been defined as the reversible nonproductive infection of a cell by a replication-competent virus (1). Several viruses have developed strategies to establish latency in the infected host to prevent their elimination by the host immune response. Varicella-Zoster virus (VZV) is an alpha herpesvirus that becomes latent in dorsal root ganglia (DRG) after primary infection and subsequently may reactivate to cause zoster. It is essential to understand the molecular mechanisms governing VZV latency and reactivation, as approximately 15% of the human population will develop zoster (2, 3) and possibly experience postherpetic neuralgia, a debilitating pain syndrome associated with zoster (4).A controversy regarding the localization of latent VZV (5-8) was resolved by the demonstration that VZV DNA is present both in neurons and satellite cells (9). The percentage of cells within an affected ganglion that are latently infected with VZV has been reported to range from 0.01% to 30% (5, 7, 9-11).Despite a wealth of data indicating that the virus immediate early (IE) proteins IE62, IE63, IE4, and the putative IE gene product ORF61p, are involved in the regulation of VZV gene expression during productive infection (12-17), little is known about the behavior of the virus during latency and the conditions that cause its reactivation. Others have shown that transcription of some VZV genes occurs in human ganglia harboring latent virus as evidenced by the presence of virus specific transcripts for ORFs 21,29, 62, and 63 (7,8,[18][19][20]. Although there is some uncertainty whether VZV latencyassociated transcription takes place in nonneuronal satellite cells or in neurons, it is clear that both IE and putative early (E) VZV genes are transcribed during latency (5-8). One of the IE gene transcripts, that for ORF63, is translated during latency, and the IE63 protein has been detected in the cytoplasm of latently infected human neurons (21) and in the cytoplasm a...

Estimates of vaccine efficacy decreased over time in the LTPS population compared with modeled control estimates. Statistically significant vaccine efficacy for HZ BOI persisted into year 10 postvaccination, whereas statistically significant vaccine efficacy for incidence of HZ persisted only through year 8.