Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit all?

In a multi-hospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

A Phase 2 Clinical Trial to Evaluate the Safety, Reactogenicity, and Immunogenicity of Different Prime-Boost Vaccination Schedules of 2013 and 2017 A(H7N9) Inactivated Influenza Virus Vaccines Administered With and Without AS03 Adjuvant in Healthy US Adults.

INTRODUCTION: A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. METHODS: Healthy adults (n = 180), ages 19-50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 µg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. RESULTS: Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6-212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. CONCLUSIONS: Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807.

Proposing the "Continuum of UTI" for a Nuanced Approach to Diagnosis and Management of Urinary Tract Infections.

PURPOSE: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach. MATERIALS AND METHODS: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme. RESULTS: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms. CONCLUSIONS: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.

Safety and Immunogenicity of Influenza A/H5N8 Virus Vaccine in Healthy Adults: Durability and Cross-reactivity of Antibody Responses.

BACKGROUND: Influenza A/H5N8 viruses infect poultry and wild birds in many countries. In 2021, the first human A/H5N8 cases were reported. METHODS: We conducted a phase I, cohort-randomized, double-blind, controlled trial of inactivated influenza A/H5N8 vaccine (clade 2.3.4.4c) administered with or without adjuvant. Cohort 1 subjects received either two doses of AS03-adjuvanted vaccine containing 3.75 µg or 15 µg hemagglutinin (HA); two doses of 15 µg HA unadjuvanted vaccine; or one dose of AS03-adjuvanted vaccine (3.75 µg or 15 µg HA), followed by one dose of non-adjuvanted vaccine (same HA content). Cohort 2 subjects received two doses of MF59-adjuvanted vaccine containing 3.75 µg or 15 µg HA, or 15 µg HA of non-adjuvanted vaccine. Subjects were followed for 13 months for safety and immunogenicity. RESULTS: We enrolled 386 adult subjects in good health. Solicited adverse events were generally mild and more common among subjects who received adjuvanted vaccines. Antibody responses (hemagglutination inhibition or microneutralization assays) were highest in the two-dose AS03 group, followed by the one-dose AS03 group, the MF59 groups, and the non-adjuvanted groups. Antibody levels returned to baseline 12 months after the second vaccination in all groups except the 15 µg AS03-adjuvanted group. Cross-reactive antibodies to clade 2.3.4.4b strains isolated from recent human cases were demonstrated in a subset of both 15 µg adjuvanted groups. CONCLUSIONS: Two doses of influenza A/H5N8 vaccine were well-tolerated. Immunogenicity improved with receipt of two doses of adjuvanted vaccine and higher antigen content. (Funded by the National Institute of Allergy and Infectious Diseases.

Immunogenicity of adjuvanted versus high-dose inactivated influenza vaccines in older adults: a randomized clinical trial.

BACKGROUND: Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. RESULTS: The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, - 5.8%; 95%CI, - 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. CONCLUSIONS: Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03183908.

Partnering to cope with pain: A pilot study of a caregiver-assisted pain coping skills intervention for patients with cognitive impairment and dementia.

OBJECTIVE: To develop a new caregiver-assisted pain coping skills training protocol specifically tailored for community-dwelling persons with cognitive impairment and pain, and assess its feasibility and acceptability. METHOD: In Phase I, we conducted interviews with 10 patient-caregiver dyads to gather feedback about intervention content and delivery. Phase II was a single-arm pilot test to evaluate the intervention's feasibility and acceptability. Dyads in the pilot study (n = 11) completed baseline surveys, received five intervention sessions, and then completed post-intervention surveys. Analyses focused on feasibility and acceptability. RESULTS: Dyads responded positively to the pain coping skills presented in the interviews; their feedback was used to refine the intervention. Findings from the pilot study suggested that the intervention was feasible and acceptable. 69% of eligible dyads consented, 82% completed all five intervention sessions, and 100% completed the post-treatment assessment. Caregivers reported high satisfaction ratings. They also reported using the pain coping skills on a regular basis, and that they found most of the skills helpful and easy to use. SIGNIFICANCE OF RESULTS: These preliminary findings suggest that a caregiver-assisted pain coping skills intervention is feasible and acceptable, and that it may be a promising approach to managing pain in patients with cognitive impairment.

The Urinary Microbiome in Postmenopausal Women with Recurrent Urinary Tract Infections.

PURPOSE: The etiology of postmenopausal recurrent urinary tract infection (UTI) is not completely known, but the urinary microbiome is thought to be implicated. We compared the urinary microbiome in menopausal women with recurrent UTIs to age-matched controls, both in the absence of acute infection. MATERIALS AND METHODS: This is a cross-sectional analysis of baseline data from 64 women enrolled in a longitudinal cohort study. All women were using topically applied vaginal estrogen. Women >55 years of age from the following groups were enrolled: 1) recurrent UTIs on daily antibiotic prophylaxis, 2) recurrent UTIs not on antibiotic prophylaxis and 3) age-matched controls without recurrent UTIs. Catheterized urine samples were collected at least 4 weeks after last treatment for UTI and at least 6 weeks after initiation of vaginal estrogen. Samples were evaluated using expanded quantitative urine culture (EQUC) and 16S rRNA gene sequencing. RESULTS: With EQUC, there were no significant differences in median numbers of microbial species isolated among groups (p=0.96), even when considering Lactobacilli (p=0.72). However, there were trends toward different Lactobacillus species between groups. With 16S rRNA sequencing, the majority of urine samples contained Lactobacillaceae, with nonsignificant trends in relative abundance among groups. Using a Bayesian analysis, we identified significant differences in anaerobic taxa associated with phenotypic groups. Most of these differences centered on Bacteroidales and the family Prevotellaceae, although differences were also noted in Actinobacteria and certain genera of Clostridiales. CONCLUSIONS: Associations between anaerobes within the urinary microbiome and postmenopausal recurrent UTI warrants further investigation.

Does a lack of vaccine side effects correlate with reduced BNT162b2 mRNA vaccine response among healthcare workers and nursing home residents?

BACKGROUND: The BNT162b2 SARS-CoV-2 mRNA vaccination has mitigated the burden of COVID-19 among residents of long-term care facilities considerably, despite being excluded from the vaccine trials. Data on reactogenicity (vaccine side effects) in this population are limited. AIMS: To assess reactogenicity among nursing home (NH) residents. To provide a plausible proxy for predicting vaccine response among this population. METHODS: We enrolled and sampled NH residents and community-dwelling healthcare workers who received the BNT162b2 mRNA vaccine, to assess local or systemic reactogenicity and antibody levels (immunogenicity). RESULTS: NH residents reported reactions at a much lower frequency and lesser severity than the community-dwelling healthcare workers. These reactions were mild and transient with all subjects experiencing more local than systemic reactions. Based on our reactogenicity and immunogenicity data, we developed a linear regression model predicting log-transformed anti-spike, anti-receptor-binding domain (RBD), and neutralizing titers, with a dichotomous variable indicating the presence or absence of reported reactions which revealed a statistically significant effect, with estimated shifts in log-transformed titers ranging from 0.32 to 0.37 (all p < 0.01) indicating greater immunogenicity in subjects with one or more reported reactions of varying severity. DISCUSSION: With a significantly lower incidence of post-vaccination reactions among NH residents as reported in this study, the BNT162b2 mRNA vaccine appears to be well-tolerated among this vulnerable population. If validated in larger populations, absence of reactogenicity could help guide clinicians in prioritizing vaccine boosters. CONCLUSIONS: Reactogenicity is significantly mild among nursing home residents and overall, subjects who reported post-vaccination reactions developed higher antibody titers.

The Effect of Age on the Immunogenicity of the Live Attenuated Zoster Vaccine Is Predicted by Baseline Regulatory T Cells and Varicella-Zoster Virus-Specific T Cell Immunity.

Older age is associated with increased infectious morbidity and decreased immune responses to vaccines, but the mechanisms that mediate this effect are incompletely understood. The efficacy and immunogenicity of the live attenuated zoster vaccine (ZVL) have a very-well-described negative association with the age of the vaccinee. In a study of 600 ZVL recipients 50 to >80 years of age, we investigated immunological factors that might explain the effect of age on the immunogenicity of ZVL. Using FluoroSpot assays and flow cytometry, we determined that varicella-zoster virus (VZV)-specific peak T helper 1 (VZV-Th1) responses to ZVL were independently predicted by prevaccination VZV-Th1 responses, regulatory T cells (Treg), and PD1-expressing immune checkpoint T cells (Tcheck) but not by the age of the vaccinee. Persistence of VZV-Th1 1 year after vaccination was independently predicted by the factors mentioned above, by peak VZV-Th1 responses to ZVL, and by the age of the vaccinee. We further demonstrated by ex vivo blocking experiments the mechanistic role of PD1 and CTLA4 as modulators of decreased VZV-Th1 responses in the study participants. VZV-specific cytotoxic T cell (VZV-CTL) and T follicular helper responses to ZVL did not correlate with age, but similar to other Th1 responses, VZV-CTL peak and baseline responses were independently correlated. These data expand our understanding of the factors affecting the magnitude and kinetics of T cell responses to ZVL in older adults and show the importance of prevaccination Treg and Tcheck in modulating the immunogenicity of ZVL. This presents new potential interventions to increase vaccine responses in older adults.IMPORTANCE Vaccination is the most effective method to protect older adults against viral infections. However, the immunogenicity of viral vaccines in older adults is notoriously poor. The live attenuated zoster vaccine (ZVL) provides the best example of a gradual decrease of vaccine immunogenicity with every 10-year age increase above 50 years. Here we show that the abundance of regulatory T cells before vaccine administration to older adults has a significant inhibitory effect on immune responses to ZVL and, together with baseline immunity to varicella-zoster virus, explains the effect of age on the immunogenicity of ZVL. Moreover, in vitro blockade of regulatory T cell mechanisms of action with biologic modulators restores immune responses to varicella-zoster virus in vaccinees. Collectively, these observations suggest that immune modulators that block regulatory T cell activity may increase responses to viral attenuated vaccines in older adults.

Discharge Information and Support for Patients Discharged from the Emergency Department: Results from a Randomized Controlled Trial.

BACKGROUND: Little research has been done on primary care-based models to improve health care use after an emergency department (ED) visit. OBJECTIVE: To examine the effectiveness of a primary care-based, nurse telephone support intervention for Veterans treated and released from the ED. DESIGN: Randomized controlled trial with 1:1 assignment to telephone support intervention or usual care arms (ClinicalTrials.gov: NCT01717976). SETTING: Department of Veterans Affairs Health Care System (VAHCS) in Durham, NC. PARTICIPANTS: Five hundred thirteen Veterans who were at high risk for repeat ED visits. INTERVENTION: The telephone support intervention consisted of two core calls in the week following an ED visit. Call content focused on improving the ED to primary care transition, enhancing chronic disease management, and educating Veterans and family members about VHA and community services. MAIN MEASURES: The primary outcome was repeat ED use within 30 days. KEY RESULTS: Observed rates of repeat ED use at 30 days in usual care and intervention groups were 23.1% and 24.9%, respectively (OR = 1.1; 95% CI = 0.7, 1.7; P = 0.6). The intervention group had a higher rate of having at least 1 primary care visit at 30 days (OR = 1.6, 95% CI = 1.1-2.3). At 180 days, the intervention group had a higher rate of usage of a weight management program (OR = 3.5, 95% CI = 1.6-7.5), diabetes/nutrition (OR = 1.8, 95% CI = 1.0-3.0), and home telehealth services (OR = 1.7, 95% CI = 1.0-2.9) compared with usual care. CONCLUSIONS: A brief primary care-based nurse telephone support program after an ED visit did not reduce repeat ED visits within 30 days, despite intervention participants' increased engagement with primary care and some chronic disease management services. TRIALS REGISTRATION: ClinicalTrials.gov NCT01717976.

Age matters: older age as a risk factor for CMV reactivation in the CMV serostatus-positive kidney transplant recipient.

Evaluate risk factors for cytomegalovirus (CMV) reactivation during the first year after kidney transplantation in the CMV-seropositive older recipient. Retrospective single-center study. Between 2011 and 2015, 91 patients ≥ 65 years received a kidney transplant; these were matched with 91 controls, aged 40-60. Risk of CMV reactivation in the CMV-seropositive recipients was analyzed. Sixty-three older and 54 younger recipients were included; 50% had received CMV-directed prophylaxis. CMV reactivation was significantly more frequent in the older group (71.4% vs 44.4%, p = 0.003) and occurred earlier (p = 0.003). A multivariate model showed that only age was associated with CMV reactivation (OR 2.48, p = 0.03). After excluding patients that received thymoglobulin, older age group remained the only risk factor of CMV reactivation (OR 3.81, p = 0.014). Recurrent event analysis showed that the older cohort had an HR of 1.94 (p = 0.01) of CMV viremia; there was significant episode-cohort interaction (p < 0.01). While the older group had a higher risk of infection (HR = 2.43), after the initial episode the relative hazards were approximately equal (HR = 1.08, at period 2). This suggests that it is key to specifically avoid the first episode of reactivation. Universal prophylaxis or a hybrid prophylaxis model should be considered in the CMV-seropositive kidney transplant recipient aged ≥ 65 years.

Persistence of Varicella-Zoster Virus Cell-Mediated Immunity After the Administration of a Second Dose of Live Herpes Zoster Vaccine.

Protection against zoster conferred by zoster vaccine live (ZVL; Zostavax) wanes over time. We compared varicella-zoster virus cell-mediated immunity (VZV-CMI) of adults ≥70 years who received a second dose of ZVL ≥10 years after the initial dose with de novo-immunized age-matched controls. Before and during the first year after vaccination, VZV-CMI was significantly higher in reimmunized compared with de novo vaccinees. At 3 years, VZV-CMI differences between groups decreased and only memory responses remained marginally higher in reimmunized participants. In conclusion, the increase in VZV-CMI generated by reimmunization with ZVL is at least equally persistent compared with de novo immunization.

Infections after kidney transplantation. Does age matter?

Infections threaten successful outcomes after kidney transplantation. Our aim was to determine if the number, types of infections and the risk factors for common infections differed between older compared to younger kidney transplant (KT) recipients in the first year after surgery. We performed a single-center retrospective cohort study. Between 2011 and 2015, 91 KTs were performed in patients ≥65 years of age; these were matched 1:1 (by year of transplantation, sex and race) to controls aged 40-60 years. Over 90% of both groups had an infectious complication. Urinary tract infections (UTIs) and cytomegalovirus (CMV) viremia were significantly more frequent in older recipients. Older adults had more late onset UTIs, including after stent removal. CMV viremia was more frequent in older adults in the 1-6 months post-transplant period. Due to our center-specific protocol utilizing pre-emptive monitoring in the CMV recipient-seropositive population, the higher CMV incidence in the aged recipient was driven by this subpopulation of older adults. No difference in pneumonias or bloodstream infections were found, nor in surgical complications, rejection or graft loss. Mortality was higher at 1-year post-transplant in the older recipients (9.9% vs 1.1%; P = 0.018). Prophylactic and immunosuppressive strategies may need to be altered for older KT recipients.

Single-center analysis of infectious complications in older adults during the first year after kidney transplantation.

Infections are among the top three causes of death of older adults in the first year after kidney transplantation (KT). Our aim was to describe infectious complications among KT recipients aged ≥ 65 during the first 12 months post-transplant. Single-center retrospective cohort study. Ninety-one KTs had been performed in patients ≥ 65 years of age between 2011 and 2015. 92.3% of the patients developed at least one infection. Infectious episodes increased the risk of future infection by 10% (p = 0.0018) with each infection portending a greater risk. At a patient level, viral (71.4%) and bacterial (70.2%) infections predominated. Urinary tract infections were the most frequent complication (30.3%), followed by cytomegalovirus infections (22.7%). Infections were the main reason for readmission. 7.7% of the patients developed rejection; and overall 3.3% lost their graft. Mortality at 1 year was 9.9%. Older KT recipients have a high incidence of infectious complications the first year after KT. Infections were the number one reason for readmission, and an infection episode predicted future infections for the individual patient. Despite these complications, the majority of older KT recipients were alive with a functioning graft at 1 year.

Poor Immunogenicity, Not Vaccine Strain Egg Adaptation, May Explain the Low H3N2 Influenza Vaccine Effectiveness in 2012-2013.

Background: Influenza vaccination aims to prevent infection by influenza virus and reduce associated morbidity and mortality; however, vaccine effectiveness (VE) can be modest, especially for subtype A(H3N2). Low VE has been attributed to mismatches between the vaccine and circulating influenza strains and to the vaccine's elicitation of protective immunity in only a subset of the population. The low H3N2 VE in the 2012-2013 season was attributed to egg-adaptive mutations that created antigenic mismatch between the actual vaccine strain (IVR-165) and both the intended vaccine strain (A/Victoria/361/2011) and the predominant circulating strains (clades 3C.2 and 3C.3). Methods: We investigated the basis of low VE in 2012-2013 by determining whether vaccinated and unvaccinated individuals were infected by different viral strains and by assessing the serologic responses to IVR-165, A/Victoria/361/2011, and 3C.2 and 3C.3 strains in an adult cohort before and after vaccination. Results: We found no significant genetic differences between the strains that infected vaccinated and unvaccinated individuals. Vaccination increased titers to A/Victoria/361/2011 and 3C.2 and 3C.3 representative strains as much as to IVR-165. These results are consistent with the hypothesis that vaccination boosted cross-reactive immune responses instead of specific responses against unique vaccine epitopes. Only approximately one-third of the cohort achieved a ≥4-fold increase in titer. Conclusions: In contrast to analyses based on ferret studies, low H3N2 VE in 2012-2013 in adults does not appear to be due to egg adaptation of the vaccine strain. Instead, low VE might have been caused by low vaccine immunogenicity in a subset of the population.

Immune response to influenza vaccination in the elderly is altered by chronic medication use.

BACKGROUND: The elderly patient population is the most susceptible to influenza virus infection and its associated complications. Polypharmacy is common in the aged, who often have multiple co-morbidities. Previous studies have demonstrated that commonly used prescription drugs can have extensive impact on immune defenses and responses to vaccination. In this study, we examined how the dynamics of immune responses to the two influenza A virus strains of the trivalent inactivated influenza vaccine (TIV) can be affected by patient's history of using the prescription drugs Metformin, NSAIDs or Statins. RESULTS: We provide evidence for differential antibody (Ab) production, B-cell phenotypic changes, alteration in immune cell proportions and transcriptome-wide perturbation in individuals with a history of long-term medication use, compared with non-users. We noted a diminished response to TIV in the elderly on Metformin, whereas those on NSAIDs or Statins had higher baseline responses but reduced relative increases in virus-neutralizing Abs (VNAs) or Abs detected by an enzyme-linked immunosorbent assay (ELISA) following vaccination. CONCLUSION: Collectively, our findings suggest novel pathways that might underlie how long-term medication use impacts immune response to influenza vaccination in the elderly. They provide a strong rationale for targeting the medication-immunity interaction in the aged population to improve vaccination responses.

Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults.

BACKGROUND: Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). METHODS: Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. RESULTS: Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. CONCLUSIONS: These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. CLINICAL TRIALS REGISTRATION: NCT01245751.

Circulating CXCR5+PD-1+ response predicts influenza vaccine antibody responses in young adults but not elderly adults.

Although influenza vaccination is recommended for all adults annually, the incidence of vaccine failure, defined as weak or absent increase in neutralizing Ab titers, is increased in the elderly compared with young adults. The T follicular helper cell (Tfh) subset of CD4 T cells provides B cell help in germinal centers and is necessary for class-switched Ab responses. Previous studies suggested a role for circulating Tfh cells (cTfh) following influenza vaccination in adults, but cTfh have not been studied in elderly adults in whom weak vaccine responses are often observed. In this study, we studied cTfh expressing CXCR5 and programmed death-1 (PD-1). cTfh from elderly adults were present at reduced frequency, had decreased in vitro B cell help ability, and had greater expression of ICOS compared with young adults. At 7 d after inactivated influenza vaccination, cTfh correlated with influenza vaccine-specific IgM and IgG responses in young adults but not in elderly adults. In sum, we have identified aging-related changes in cTfh that correlated with reduced influenza vaccine responses. Future rational vaccine design efforts should incorporate Tfh measurement as an immune correlate of protection, particularly in the setting of aging.

Herpes Zoster Vaccination: Controversies and Common Clinical Questions.

Herpes zoster, clinically referred to as shingles, is an acute, cutaneous viral infection caused by reactivation of the varicella zoster virus, the same virus that causes chickenpox. The incidence of herpes zoster and its complications increase with decline in cell-mediated immunity, including age-associated decline. The most effective management strategy for herpes zoster is prevention of the disease through vaccination in those who are most vulnerable. Despite the demonstrated efficacy in reducing the incidence and severity of herpes zoster, the uptake of vaccine remains low. Here, we will discuss the controversies that surround the live herpes zoster vaccine and address the common clinical questions that arise. We will also discuss the new adjuvanted herpes zoster vaccine currently under investigation.