Seasonal influenza virus vaccines are generally effective at preventing disease, but need to be well matched to circulating virus strains for maximum benefit. Influenza viruses constantly undergo antigenic changes because of their high mutation rate in the immunodominant haemagglutinin (HA) head domain, which necessitates annual re-formulation and re-vaccination for continuing protection. In case of pandemic influenza virus outbreaks, new vaccines need to be produced and quickly distributed. Novel influenza virus vaccines that redirect the immune response towards more conserved epitopes located in the HA stalk domain may remove the need for annual vaccine re-formulation and could also protect against emergent pandemic strains to which the human population is immunologically naive. One approach to create such universal influenza virus vaccines is the use of constructs expressing chimeric HAs. By sequential immunization with vaccine strains expressing the same conserved HA stalk domain and exotic HA heads to which the host is naive, antibodies against the stalk can be boosted to high titres. Here we tested a monovalent chimeric HA-based prototype universal influenza virus split virion vaccine candidate with and without AS03 adjuvant in primed mice. We found that the chimeric HA-based vaccination regimen induced higher stalk antibody titres than the seasonal vaccine. The stalk antibody responses were long lasting, cross-reactive to distantly related HAs and provided protection in vivo in a serum transfer challenge model. The results of this study are promising and support further development of a universal influenza vaccine candidate built on the chimeric HA technology platform.
GSK has developed a two-dose adjuvanted recombinant zoster vaccine (Shingrix, RZV) to protect people aged ≥50 years (50+) against herpes zoster (HZ) and its complications. RZV showed >90% efficacy against HZ, sustained over 4 years of follow-up, in all studied age groups. Areas covered: This article reviews the scientific rationale underlying the design of RZV; the clinical evidence demonstrating immunogenicity, safety, and efficacy in persons 50+; and the public health implications and cost-effectiveness. Expert commentary: A decline in varicella zoster virus (VZV) immunity is associated with increased risk of HZ in adults 50+ and immunocompromised individuals. RZV was designed to restore levels of anti-VZV cellular and humoral immunity to prevent VZV reactivation. RZV includes the recombinant gE glycoprotein antigen, and Adjuvant System AS01 which promotes cellular and antibody responses. In two Phase III studies in subjects aged 50+ and 70+ years, RZV efficacy against HZ compared to placebo was >90% and ≥89% against post-herpetic neuralgia (PHN). RZV is expected to dramatically impact HZ morbidity including its complications, and associated health-care costs. In the US population aged 50+ years, vaccination with RZV can be cost-effective compared to no vaccination and cost-saving compared to the currently available live-attenuated HZ vaccine (Zostavax, Merck).
Herpes zoster (HZ) is associated with substantial morbidity. It is caused by reactivation of the latent varicella zoster virus (VZV) following decline in cell-mediated immunity, which is commonly age-related, but also occurs in individuals with immunosuppressive diseases and/ or treatment. Since coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has been associated with T cell immune dysfunction and there have been reports of HZ in COVID-19 patients, we have performed a review of available literature on whether COVID-19 could trigger HZ. We identified 27 cases of HZ following COVID-19, which most frequently occurred within 1-2 weeks of COVID-19, and the majority of cases had typical presentation. Atypical presentations of HZ were noted especially in patients with lymphopenia. It has been hypothesized that VZV reactivation occurs as a consequence of T cell dysfunction (including lymphopenia and lymphocyte exhaustion) in COVID-19 patients. Based on current evidence, which is limited to case reports and case series, it is not possible to determine whether COVID-19 increases the risk of HZ. Practitioners should be aware of the possible increased risk of HZ during the pandemic period and consider timely therapeutic and preventive measures against it.
Introduction:The adjuvanted recombinant zoster vaccine (RZV) is currently licensed in over 30 countries for the prevention of herpes zoster (HZ) in adults aged ≥50 years. We conducted a review of available national guidelines or recommendations on RZV use to identify the similarities and differences and highlight any potential gaps. Areas covered: National recommendations from ten countries (Austria, Canada,
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