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Immune responses were measured using assays of anti-spike protein IgG and neutralising antibody titres for humoral immunity and IFN-γ enzyme-linked immunospot (ELISpot) for cell-mediated immunity. In IFN-γ ELISpot assays enumerating antigen-specific T cells done for those in the prime-boost standard-dose group, T-cell responses peaked at 14 days after a single standard dose and did not increase significantly after a boost dose (18–55 years, median 1187 spot forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841–2428], n=24; 56–69 years, 797 SFCs [383–1817], n=29; and ≥70 years 977 SFCs [458–1914], n=48; p=0·46). The inclusion of measures of cell-mediated immunity is important given the limitations of relying solely on antibody titres in older adults.4,5 The main study limitations were its single-blind design, the inclusion of few participants older than 80 years, and exclusion of people with substantial underlying chronic illnesses and frailty.

In this randomized, controlled trial involving more than 15,000 participants 50 years of age or older, a varicella–zoster virus subunit vaccine with AS01B adjuvant was found to have an efficacy of more than 96% in preventing herpes zoster. Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) in the dorsal-root or cranial-nerve ganglia, usually decades after primary infection. 1 , 2 Herpes zoster is characterized by a vesicular rash with a unilateral and dermatomal distribution and is almost always accompanied by pain. More than 90% of adults have been infected with VZV and are at risk for herpes zoster. 3 , 4 Although herpes zoster is most frequent in adults who are 50 years of age or older owing to immunosenescence, it can occur at any age, especially when cell-mediated immunity is decreased as a result of disease . . .

Background. Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty. Methods. We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011–2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty. Results. Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%–73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%–73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased. Conclusions. Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased.

Although influenza is primarily considered a respiratory infection and causes significant respiratory mortality, evidence suggests that influenza has an additional burden due to broader consequences of the illness. Some of these broader consequences include cardiovascular events, exacerbations of chronic underlying conditions, increased susceptibility to secondary bacterial infections, functional decline, and poor pregnancy outcomes, all of which may lead to an increased risk for hospitalization and death. Although it is methodologically difficult to measure these impacts, epidemiological and interventional study designs have evolved over recent decades to better take them into account. Recognizing these broader consequences of influenza virus infection is essential to determine the full burden of influenza among different subpopulations and the value of preventive approaches. In this review, we outline the main influenza complications and societal impacts beyond the classical respiratory symptoms of the disease.

To evaluate the effectiveness of a nurse-led hospital-to-home transitional care intervention versus usual care on mental functioning (primary outcome), physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use costs in older adults with multimorbidity ([greater than or equal to] 2 comorbidities) and depressive symptoms. Pragmatic multi-site randomized controlled trial conducted in three communities in Ontario, Canada. Participants were allocated into two groups of intervention and usual care (control). 127 older adults ([greater than or equal to] 65 years) discharged from hospital to the community with multimorbidity and depressive symptoms. This evidence-based, patient-centred intervention consisted of individually tailored care delivery by a Registered Nurse comprising in-home visits, telephone follow-up and system navigation support over 6-months. The primary outcome was the change in mental functioning, from baseline to 6-months. Secondary outcomes were the change in physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use cost, from baseline to 6-months. Intention-to-treat analysis was performed using ANCOVA modeling. Of 127 enrolled participants (63-intervention, 64-control), 85% had six or more chronic conditions. 28 participants were lost to follow-up, leaving 99 (47 -intervention, 52-control) participants for the complete case analysis. No significant group differences were seen for the baseline to six-month change in mental functioning or other secondary outcomes. Older adults in the intervention group reported receiving more information about health and social services (p = 0.03) compared with the usual care group. Although no significant group differences were seen for the primary or secondary outcomes, the intervention resulted in improvements in one aspect of patient experience (information about health and social services). The study sample fell below the target sample (enrolled 127, targeted 216), which can account for the non-significant findings. Further research on the impact of the intervention and factors that contribute to the results is recommended.

The seroprotection rate (SPR) of hepatitis B vaccination in adults is suboptimal. The aim of this study was to compare the SPR of a tri-antigenic hepatitis B vaccine (TAV), with a mono-antigenic vaccine (MAV) in adults of all ages. This was a multicentre, double-blind, phase 3, randomised controlled trial (PROTECT) comparing the immunogenicity and safety of TAV with MAV in 28 community and hospital sites in the USA, Finland, Canada, and Belgium. Adults (aged ≥18 years) seronegative for hepatitis B virus (HBV), including those with well-controlled common chronic conditions, were randomly assigned (1:1) and stratified by study centre and age according to a web-based permuted blocked randomisation. Participants received either TAV or MAV which were administered as an intramuscular dose (1 mL) of TAV (10 μg; Sci-B-Vac, VBI Vaccines [SciVac, Rehovot, Israel]) or MAV (20 μg; Engerix-B [GlaxoSmithKline Biologicals, Rixensart, Belgium]) on days 0, 28, and 168 with six study visits and 24 weeks of follow-up after the third vaccination. Participants, investigators, and those assessing outcomes were masked to group assignment. The co-primary outcomes were to show non-inferiority of the SPRs 4 weeks after the third vaccination with TAV versus MAV in adults aged 18 years and older, as well as superiority in adults aged 45 years and older. SPR was defined as the percentage of participants attaining anti-HBs titres of 10 mIU/mL or higher. Non-inferiority of TAV to MAV was concluded if the lower limit of the 95% CI for the between-group difference was greater than −5%. Non-inferiority was assessed in the per-protocol set of participants (aged ≥18 years) and superiority was assessed in all participants (aged ≥45 years) who received at least one vaccination and had at least one evaluable immunogenicity sample after baseline (full analysis set). Safety analyses were a secondary outcome and included all participants who received at least one injection. This trial is registered at Clinicaltrials.gov (NCT03393754) and EudraCT (2017–001819–36) and is closed to new participants. Between Dec 13, 2017, and April 8, 2019, 1607 participants (796 allocated to TAV and 811 allocated to MAV) were randomly assigned and distributed across age cohorts of 18–44 years (299 of 1607; 18·6%), 45–64 years (716 of 1607; 44·6%), and 65 years and older (592 of 1607; 36·8%). In participants aged 18 years and older, SPR was 91·4% (656 of 718) in the TAV group versus 76·5% (553 of 723) in the MAV group (difference 14·9%, 95% CI 11·2–18·6), showing non-inferiority in the per-protocol set. In participants aged 45 years and older, SPR was 89·4% (559 of 625) in the TAV group versus 73·1% (458 of 627) in the MAV group (difference 16·4%, 95% CI 12·2–20·7), showing superiority in the full analysis set. TAV was associated with higher rates of mild or moderate injection site pain (63·2% [503 of 796] in TAV vs 36·3% [294 of 811] in MAV), tenderness (60·8% [484 of 796] in TAV vs 34·8% [282 of 811] in MAV), and myalgia (34·7% [276 of 796] vs 24·3% [197 of 811] in MAV). Otherwise, the safety profile of TAV was similar to that of MAV. The safety and efficacy of TAV shows its usefulness for the prevention of HBV infection in adults, including those with stable and controlled chronic conditions. VBI Vaccines.

Abstract Background The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration NCT01165177; NCT01165229. The herpes zoster subunit vaccine, consisting of varicella-zoster virus glycoprotein E and the AS01B Adjuvant System, stimulated specific antibody and CD4 T-cell responses in >90% of recipients which, in most, persisted for the 36-month duration of the study.

Despite widespread influenza vaccination programs, influenza remains a major cause of morbidity and mortality in older adults. Age-related changes in multiple aspects of the adaptive immune response to influenza have been well-documented including a decline in antibody responses to influenza vaccination and changes in the cell-mediated response associated with immune senescence. This review will focus on T cell responses to influenza and influenza vaccination in older adults, and how increasing frailty or coexistence of multiple (≥2) chronic conditions contributes to the loss of vaccine effectiveness for the prevention of hospitalization. Further, dysregulation of the production of pro- and anti-inflammatory mediators contributes to a decline in the generation of an effective CD8 T cell response needed to clear influenza virus from the lungs. Current influenza vaccines provide only a weak stimulus to this arm of the adaptive immune response and rely on re-stimulation of CD8 T cell memory related to prior exposure to influenza virus. Efforts to improve vaccine effectiveness in older adults will be fruitless until CD8 responses take center stage.

Background. Few studies have prospectively assessed viral etiologies of acute respiratory infections in communitybased elderly individuals. We assessed viral respiratory pathogens in individuals > 65 years with influenza-like illness (ILI). Methods. Multiplex reverse-transcriptase polymerase chain reaction identified viral pathogens in nasal/throat swabs from 556 episodes of moderate-to-severe ILI, defined as ILI with pneumonia, hospitalization, or maximum daily influenza symptom severity score (ISS) ≥ 2. Cases were selected from a randomized trial of an adjuvanted vs nonadjuvanted influenza vaccine conducted in elderly adults from 15 countries. Results. Respiratory syncytial virus (RSV) was detected in 7.4% (41/556) moderate-to-severe ILI episodes in elderly adults. Most (39/41) were single infections. There was a significant association between country and RSV detection (P = .004). RSV prevalence was 7.1% (2/28) in ILI with pneumonia, 12.5% (8/64) in ILI with hospitalization, and 6.7% (32/480) in ILI with maximum ISS > 2. Any virus was detected in 320/556 (57.6%) ILI episodes: influenza A (104/556, 18.7%), rhinovirus/enterovirus (82/556, 14.7%), coronavirus and human metapneumovirus (each 32/556, 5.6%). Conclusions. This first global study providing data on RSV disease in > 65 year-olds confirms that RSV is an important respiratory pathogen in the elderly. Preventative measures such as vaccination could decrease severe respiratory illnesses and complications in the elderly.

In this trial of a recombinant VZV glycoprotein E subunit vaccine with the adjuvant AS01 B , the risk of herpes zoster and postherpetic neuralgia is shown to be significantly lower in association with the vaccine than with placebo among persons 70 years of age or older. Herpes zoster, or shingles, results from the reactivation of latent varicella–zoster virus (VZV) and typically manifests as a vesicular, painful dermatomal rash. 1 , 2 The most common complication of herpes zoster, postherpetic neuralgia, manifests as chronic neuropathic pain that can greatly limit daily activities. 1 , 3 – 6 The overall incidence of herpes zoster is 2.0 to 4.6 cases per 1000 person-years but increases with age to 10.0 to 12.8 per 1000 person-years among persons 80 years of age or older. 7 – 10 Similarly, the incidence of postherpetic neuralgia also increases with age. 10 – 13 Antiviral therapy can reduce the duration of herpes zoster rash . . .