Varicella and herpes zoster vaccine development: lessons learned

Abstract

Introduction: Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines’ efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

The beneficial effects of varicella zoster virus

“…-Ramsay Hunt syndrome: lower motor neuron facial palsy with nausea,vomiting, tinnitus, hearing loss, vertigo and nystagmus. endemic worldwide [153]. Developments in varicella and HZ vaccines which require a better understanding of the host response to VZV can offer the potential to prevent the majority of VZV infections [150,153].…”

“…endemic worldwide [153]. Developments in varicella and HZ vaccines which require a better understanding of the host response to VZV can offer the potential to prevent the majority of VZV infections [150,153]. The implementation of universal varicella vaccination in many areas around the globe >20 years ago has resulted in a signi icant reduction in the burden of varicella-associated disease [154].…”

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“…After transmission to a susceptible host, VVZ proliferates in the oropharynx, infects T cells and produces a first viremia; T cells transport the virus into the skin and other organs. The infection is initially controlled by innate immunity that slows viral multiplication at the epidermal level and thus allows adaptive immunity to develop (21).…”

“…VVZ-specific T cells, which are essential to stop the viremic phase and to allow varicella healing, become detectable 1-3 days after the rash occurs. These VVZ-specific T-cells target antigens that include glycoprotein gE of VVZ, protein 62 and other viral proteins (21). The severity of the infection is inversely correlated with the rapidity of T cell proliferation and the intensity of this response.…”

Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

“…The human herpesviruses are responsible for a wide range of pathologies and, currently, effective vaccination is available for only one of them, the varicella-zoster virus [8]. In this short review, the roles of CMV and EBV will be described in two diseases of neurological interest.…”