Absenteeism and Productivity Loss Due to Influenza or Influenza-like Illness in Adults in Europe and North America.

Healthy working-age adults are susceptible to illness or caregiving requirements resulting from annual seasonal influenza, leading to considerable societal and economic impacts. The objective of this targeted narrative review is to understand the societal burden of influenza in terms of absenteeism and productivity loss, based on the current literature. This review includes 48 studies on the impact of influenza and influenza-like illness (ILI) and reports on the effect of influenza vaccination, age, disease severity, caring for others, comorbidities, and antiviral prophylaxis on absenteeism and productivity loss due to influenza/ILI, focusing on publications originating from Canada, Europe, and the United States.

Trained Immunity Generated by the Recombinant Zoster Vaccine.

Trained immunity may play a role in vaccine-induced protection against infections. We showed that the highly efficacious recombinant VZV-gE zoster vaccine (RZV) generated trained immunity in monocytes, natural killer (NK) cells, and dendritic cells (DCs) and that the less efficacious live zoster vaccine did not. RZV stimulated ex vivo gE-specific monocyte, DC and NK cell responses that did not correlate with CD4 + T-cell responses.

The economic rationale for cell-based influenza vaccines in children and adults: A review of cost-effectiveness analyses.

Seasonal influenza significantly affects both health and economic costs in children and adults. This narrative review summarizes published cost-effectiveness analyses (CEAs) of cell-based influenza vaccines in children and adults <65 years of age, critically assesses the assumptions and approaches used in these analyses, and considers the role of cell-based influenza vaccines for children and adults. CEAs from multiple countries demonstrated the cost-effectiveness of cell-based quadrivalent influenza vaccines (QIVc) compared with egg-based trivalent/quadrivalent influenza vaccines (TIVe/QIVe).

Effect of high dose vitamin D supplementation on subsequent immune responses to administration of the live herpes zoster vaccine to long-term care residents.

Thirty-three long-term care residents (mean age 76.5 years), who were participating in a study in which they were randomized to receive either oral daily standard dose (400-1000 IU/day) 25-hydroxy vitamin D (vitamin D3) (SD) or high dose (3000-4000 IU/day) (HD) vitamin D3, were vaccinated with the live, attenuated herpes zoster vaccine. Blood was drawn at vaccination and three weeks later to determine varicella-zoster virus (VZV) antibody and T-cell mediated immune responses.

Innate and Adaptive Cell-Mediated Immune Responses to a COVID-19 mRNA Vaccine in Young Children.

Background: There is little information on cell-mediated immunity (CMI) to COVID-19 mRNA vaccines in children. We studied adaptive and innate CMI in vaccinated children aged 6 to 60 months.

Methods: Blood obtained from participants in a randomized placebo-controlled trial of an mRNA vaccine before and 1 month after the first dose was used for antibody measurements and CMI (flow cytometry).

A clinical and economic assessment of adjuvanted trivalent versus standard egg-derived quadrivalent influenza vaccines among older adults in the United States during the 2018-19 and 2019-20 influenza seasons.

Background: Clinical evidence supports use of enhanced influenza vaccines in older adults. Few economic outcome studies have compared adjuvanted trivalent inactivated (aIIV3) and standard egg-derived quadrivalent inactivated influenza vaccines (IIV4e).

Research Design And Methods: A retrospective cohort study was conducted leveraging deidentified US hospital data linked to claims data during the 2018-19 and 2019-20 influenza seasons.

Recruitment of naive CD4+ T cells by the recombinant zoster vaccine correlates with persistent immunity.

Herpes zoster (HZ) is a substantial problem for people with decreased cell-mediated immunity, including older adults. The first vaccine approved for HZ prevention, the zoster vaccine live (ZVL), which provided limited and short-lived protection, has been supplanted by the superior recombinant zoster vaccine (RZV), which provides robust and durable protection. To understand the mechanisms underlying the differential immunologic characteristics of the 2 vaccines, we used T cell receptor β chain sequencing and peptide-MHC class II tetramer staining to analyze recombinant glycoprotein E-specific (gE-specific) CD4+ T cell clonotypes in RZV and ZVL recipients.

Breakthrough SARS-CoV-2 Infections in the PROVENT Prevention Trial Were Not Associated With AZD7442 (Tixagevimab/Cilgavimab) Resistant Variants.

Background: We report spike protein-based lineage and AZD7442 (tixagevimab/cilgavimab) neutralizing activity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified from breakthrough infections in the PROVENT preexposure prophylaxis trial.

Methods: Variants identified from PROVENT participants with reverse-transcription polymerase chain reaction-positive symptomatic illness were phenotypically assessed to determine neutralization susceptibility of variant-specific pseudotyped virus-like particles.

Results: At completion of 6 months' follow-up, no AZD7442-resistant variants were observed in breakthrough coronavirus disease 2019 (COVID-19) cases.

Predictors of 5-Year Persistence of Antibody Responses to Zoster Vaccines.

Background: Protection against herpes zoster is primarily conferred by cell-mediated immunity. However, anti-varicella-zoster virus (VZV) glycoprotein (anti-gp) antibody responses to zoster vaccine live (ZVL) are correlated with protection, suggesting a potential protective role for antibody. Detailed studies of antibody responses to the recombinant zoster vaccine (RZV) are provided.

Development of antibody-dependent cellular cytotoxicity in response to recombinant and live-attenuated herpes zoster vaccines.

Zoster vaccines generate antibody responses against varicella-zoster virus (VZV). We compared antibody-dependent cell cytotoxicity (ADCC) elicited by zoster vaccine live (ZVL) and recombinant zoster vaccine (RZV). ADCC mediated by antibodies against VZV lysate (VZV-ADCC) and recombinant glycoprotein E (gE-ADCC) was measured using plasma from 20 RZV- and 20 ZVL-recipients, including half 50-60-years-old and half ≥70-years-old.

Intramuscular AZD7442 (Tixagevimab-Cilgavimab) for Prevention of Covid-19.

Background: The monoclonal-antibody combination AZD7442 is composed of tixagevimab and cilgavimab, two neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that have an extended half-life and have been shown to have prophylactic and therapeutic effects in animal models. Pharmacokinetic data in humans indicate that AZD7442 has an extended half-life of approximately 90 days.

Methods: In an ongoing phase 3 trial, we enrolled adults (≥18 years of age) who had an increased risk of an inadequate response to vaccination against coronavirus disease 2019 (Covid-19), an increased risk of exposure to SARS-CoV-2, or both.

Immune Responses to Varicella-Zoster Virus Vaccines.

The live attenuated varicella vaccine is intended to mimic the tempo and nature of the humoral and cell-mediated immune responses to varicella infection. To date, two doses of varicella vaccine administered in childhood have been very effective in generating varicella-zoster virus (VZV) immune responses that prevent natural infection for at least several decades. After primary infection, the infecting VZV establishes latency in sensory and cranial nerve ganglia with the potential to reactivate and cause herpes zoster.

A Real-World Clinical and Economic Analysis of Cell-Derived Quadrivalent Influenza Vaccine Compared to Standard Egg-Derived Quadrivalent Influenza Vaccines During the 2019-2020 Influenza Season in the United States.

Background: Cell-derived influenza vaccines are not subject to egg-adaptive mutations that have potential to decrease vaccine effectiveness. This retrospective analysis estimated the relative vaccine effectiveness (rVE) of cell-derived quadrivalent influenza vaccine (IIV4c) compared to standard egg-derived quadrivalent influenza vaccines (IIV4e) among recipients aged 4-64 years in the United States during the 2019-2020 influenza season.

Methods: The IQVIA PharMetrics Plus administrative claims database was utilized.

Cell-Mediated Immune Responses After Administration of the Live or the Recombinant Zoster Vaccine: 5-Year Persistence.

We compared glycoprotein E (gE)- and varicella zoster virus (VZV)-specific Th1 immunity in 160 adults, aged 50-85 years, randomized to receive live or recombinant zoster vaccine (RZV). gE-specific responses measured by interferon-γ (IFN-γ) and interleukin 2 (IL-2) dual-color Fluorospot were significantly higher at all time points postimmunization in RZV recipients. VZV-specific IL-2+ memory, but not IFN-γ+ or IFN-γ+IL-2+ effector responses, were higher in RZV recipients at ≥3 months postimmunization.

Humoral and cellular immune responses to recombinant herpes zoster vaccine in patients with chronic lymphocytic leukemia and monoclonal B cell lymphocytosis.

Monoclonal B-cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) are clonal B-cell disorders associated with an increased risk of infections and impaired vaccination responses. We investigated the immunogenicity of recombinant zoster vaccine (RZV) in these patients. Individuals with MBL/untreated CLL and Bruton tyrosine kinase inhibitor (BTKi)-treated CLL patients were given two doses of RZV separated by 2 months.

Comparing the Clinical and Economic Outcomes Associated with Adjuvanted versus High-Dose Trivalent Influenza Vaccine among Adults Aged ≥ 65 Years in the US during the 2019-20 Influenza Season-A Retrospective Cohort Analysis.

The burden of influenza is disproportionally higher among older adults. We evaluated the relative vaccine effectiveness (rVE) of adjuvanted trivalent (aIIV3) compared to high-dose trivalent influenza vaccine (HD-IIV3e) against influenza and cardio-respiratory disease (CRD)-related hospitalizations/ER visits among adults ≥65 years during the 2019-2020 influenza season. Economic outcomes were also compared.

Association Between Immunogenicity and Reactogenicity: A Post Hoc Analysis of 2 Phase 3 Studies With the Adjuvanted Recombinant Zoster Vaccine.

A recurrent question is whether transient reactions to vaccines translate into better immune responses. Using clinical data from 2 large phase 3 studies of the recombinant zoster vaccine, we observed a small but statistically significant association between the intensity of a frequent side effect (pain) after vaccination and immune responses to vaccination. However, despite the statistical correlation, the impact on the immune response is so small, and the immune response in individuals without pain already sufficient, that pain cannot be a surrogate marker for an appropriate immune response.

Comparative Antibody Responses to the Live-Attenuated and Recombinant Herpes Zoster Vaccines.

Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ.

Vaccines for older adults.

The proportion of the global population aged 65 and older is rapidly increasing. Infections in this age group, most recently with SARS-CoV-2, cause substantial morbidity and mortality. Major improvements have been made in vaccines for older people, either through the addition of novel adjuvants-as in the new recombinant zoster vaccine and an adjuvanted influenza vaccine-or by increasing antigen concentration, as in influenza vaccines.

Recombinant Zoster Vaccine Is Efficacious and Safe in Frail Individuals.

Background/objectives: Frail participants are often under-represented in randomized trials, raising questions about outcomes of interventions in real-world settings. Frailty is strongly associated with vulnerability to illness and adverse health outcomes. We studied the impact of frailty on recombinant zoster vaccine (RZV) clinical outcomes.