Herpes zoster and the search for an effective vaccine

Abstract

SummaryPrimary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax V R is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post-herpetic neuralgia by 66Á5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immunecompetent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster.

Development of adjuvanted recombinant zoster vaccine and its implications for shingles prevention

“…The next 5 years may also see the availability of an inactivated whole virus HZ vaccine currently in development in immunosuppressed populations, investigated with administration of four vaccine doses [112,113].…”

The beneficial effects of varicella zoster virus

“…Both VZV infection and varicella vaccination can induce VZVspeci ic antibodies and T-cell mediated immunity that are essential for recovery [154]. Several countries have also adopted VZV vaccination for high-risk groups [154,155]. Despite the rare reports of breakthrough VZV infections that may become disseminated and life-threatening particularly in immune compromised hosts, VZV vaccines including the live-attenuated ones are generally safe as shown by a 10 year global safety database as well as 2 systematic literature reviews, each of which included at least 31 million doses of VZV vaccines administered [151,[156][157][158][159].…”

Varicella and herpes zoster vaccine development: lessons learned

“…It is transmitted from person to person through inhalation of virus-containing droplets and from direct contact with or aerosol transmission from infectious vesicular fluid [2,21,23]. Patients with varicella remain infectious from 1 to 2 days before the onset of rash, until around 4–5 days after rash onset when all of the lesions have formed crusts [22].…”

“…Along with herpes simplex virus types 1 and 2, VZV is part of the alpha herpesvirus family of DNA viruses. Its linear 125-kb double-stranded DNA genome encodes at least 71 unique open-reading frames (ORFs) [1], with approximately 40 conserved genes shared with other human herpesviruses [2]. The genome is located within an icosahedral capsid, surrounded by a protein tegument and encapsulated by a polyamine, lipid, and glycoprotein envelope [3].…”

“…Viral replication during infection is controlled by both innate and adaptive immune responses, with initial host defenses mediated through natural killer cells and type 1 interferons [2]. VZV-specific T cells, which are essential to terminate the viremic phase and enable recovery from varicella, become detectable one to three days after the skin rash appears [7].…”