The Advisory Committee on Immunization Practices to the US Centers for Disease Control and Prevention provides annual recommendations for routine adult immunizations. Many recommendations consider ...patient factors such as age, medical conditions, and medications that increase an individual's risk for infection with a vaccine-preventable disease. These factors, particularly those that lead to immunocompromise, may also alter the risk-benefit ratio for live vaccines, and/or lead to decreased vaccine immunogenicity and effectiveness. The provider may need to consider alternative vaccination strategies, including higher antigen dose vaccines, adjuvanted vaccines, avoidance of live vaccines, and careful timing of vaccination to optimize safety and effectiveness in immunocompromised populations. This thematic review discusses general principles regarding immunization of adults across the spectrum of immunocompromise, examines current guidelines and studies that support them, and outlines future research needs.
Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help ...to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.
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•Integrative analysis of orthogonal data on response to vaccination•Strong association between plasma metabolomics and PBMC transcriptomics•Sterol metabolism integrates cellular and humoral responses•Metabolic phenotype, such as inositol phosphate metabolism, influences immune outcome
An integrated metabolic response underlies the immune response to shingles vaccine in humans.
Tuberculosis is a major occupational hazard in low and middle-income countries. Limited data exist on serial testing of healthcare workers (HCWs) with interferon-γ release assays (IGRAs) for latent ...tuberculosis infection (LTBI), especially in low and middle-income countries. We sought to evaluate the rates of and risk factors for LTBI prevalence and LTBI test conversion among HCWs using the tuberculin skin test (TST) and QuantiFERON-TB Gold In-tube assay (QFT-GIT).
A prospective longitudinal study was conducted among HCWs in the country of Georgia. Subjects completed a questionnaire, and TST and QFT-GIT tests were performed. LTBI testing was repeated 6-26 months after baseline testing.
Among 319 HCWs enrolled, 89% reported prior BCG vaccination, and 60% worked in TB healthcare facilities (HCFs). HCWs from TB HCFs had higher prevalence of positive QFT-GIT and TST than those from non-TB HCFs: 107/194 (55%) vs. 30/125 (31%) QFT-GIT positive (p<0.0001) and 128/189 (69%) vs. 64/119 (54%) TST positive (p = 0.01). There was fair agreement between TST and QFT-GIT (kappa = 0.42, 95% CI 0.31-0.52). In multivariate analysis, frequent contact with TB patients was associated with increased risk of positive QFT-GIT (aOR 3.04, 95% CI 1.79-5.14) but not positive TST. Increasing age was associated with increased risk of positive QFT-GIT (aOR 1.05, 95% CI 1.01-1.09) and TST (aOR 1.05, 95% CI 1.01-1.10). High rates of HCW conversion were seen: the QFT-GIT conversion rate was 22.8/100 person-years, and TST conversion rate was 17.1/100 person-years. In multivariate analysis, female HCWs had decreased risk of TST conversion (aOR 0.05, 95% CI 0.01-0.43), and older HCWs had increased risk of QFT-GIT conversion (aOR 1.07 per year, 95% CI 1.01-1.13).
LTBI prevalence and LTBI test conversion rates were high among Georgian HCWs, especially among those working at TB HCFs. These data highlight the need for increased implementation of TB infection control measures.
The QuantiFERON-TB Gold Plus (QFT-Plus; Qiagen, Germantown, MD) interferon gamma release assay (IGRA) received FDA clearance in 2017 and will replace the prior version of the assay, the QFT-Gold ...In-Tube (QFT-GIT). Here, we compared performances of the QFT-Plus assay and the QFT-GIT version in a diverse patient population, including patients undergoing evaluation for or follow-up of latent tuberculosis infection (LTBI;
= 39) or active TB infection (
= 3), and in health care workers (HCWs;
= 119) at Mayo Clinic (Rochester, MN). Compared to the QFT-GIT, the QFT-Plus assay showed 91.2% (31/34) positive, 98.4% (124/126) negative, and 96.6% (156/161) overall qualitative agreement among the 161 enrolled subjects, with a Cohen's kappa value of 0.91 (excellent interrater agreement). Among the 28 patients diagnosed with LTBI at the time of enrollment, the QFT-GIT and QFT-Plus assays agreed in 24 (85.7%) patients; in all four discordant patients, the positivity of the QFT-GIT or QFT-Plus IGRA was associated with low-level interferon gamma (IFN-γ) reactivity, ranging from 0.36 IU/ml to 0.66 IU/ml. Additionally, we document a high degree of correlation between IFN-γ levels in the QFT-GIT TB antigen tube and each of the two QFT-Plus TB antigen tubes, as well as between the QFT-Plus TB1 and TB2 tubes (Pearson's correlation coefficients
> 0.95). Overall, we show comparable results between the QFT-GIT and QFT-Plus assays in our study population composed of subjects presenting with a diverse spectrum of TB infections. Our findings suggest that the necessary transition to the QFT-Plus assay will be associated with a minimal difference in assay performance characteristics.
To estimate the diagnostic prevalence of autism spectrum disorders (ASDs) in a low birth weight (LBW) cohort.
Participants belonged to a regional birth cohort of infants (N = 1105) born weighing ...<2000 g between October 1, 1984, and July 3, 1989, and followed up by periodic assessments to 21 years of age. At 16 years (n = 623), adolescents were screened for ASD using a wide net (previous professional diagnosis of an ASD or a score above a liberal cutoff on the Social Communication Questionnaire or the Autism Spectrum Symptoms Questionnaire). At 21 years (n = 189), 60% of screen positives and 24% of screen negatives were assessed for diagnoses of ASD by the Autism Diagnostic Observation Schedule or the Autism Diagnostic Interview-Revised.
Samples retained at ages 16 and 21 years were representative of samples assessed at earlier ages except for lower levels of social risk. Of positive screens, 11 of 70 had ASD; of negative screens, 3 of 119 had ASD. The fractions of the 2 screening groups with ASD (14.3% in screen-positives and 2.5% in screen negatives) were weighted by fractions of screen-positives and screen-negatives among the adolescents (18.8% and 81.2%, respectively). This calculation produced an estimated prevalence rate of ASD in the entire cohort of 5% (31 of 623).
The diagnostic prevalence of ASD in this LBW preterm cohort was higher than that reported by the Centers for Disease Control and Prevention for 8-year-olds in the general US population in 2006.
The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in ...young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y;
= 25) and older (60-80 y;
= 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4
and CD8
T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8
CD57
senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4
CD69
CD57
PD1
and CD8
CD69
CD57
PD1
T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8
effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4
and CD8
proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ.
Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine ...acceptance--and thus to infectious disease prevention--worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine AEs, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term 'adversomics' was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine AEs/reactions, and outline a plan for the further development of this emerging research field.
Older adults are disproportionately affected by influenza morbidity and mortality. In most high income countries, influenza vaccine policies target persons age ≥65 years for influenza vaccination. ...Many low-resource settings do not utilize seasonal influenza vaccination. Barriers to influenza prevention among older adults around the globe are multiple and some vary between high- and low-resource settings. To maximize influenza prevention in the older adult population, gaps in influenza vaccination coverage and improvements in vaccine efficacy are needed. The focus of this article is on the data for currently available vaccine strategies to maximize influenza vaccine impact, with a focus on high-resource settings. We also discuss novel influenza vaccine strategies needed for older adults worldwide.
Summary HIV and hepatitis B virus co-infection leads to substantially increased morbidity and mortality compared with either infection alone. Immunisation with hepatitis B virus vaccine is the most ...effective way to prevent the infection in people with HIV; however, these patients have decreased vaccine responses and a short duration of protection compared with immunocompetent individuals. Control of HIV replication with highly active antiretroviral therapy and increased CD4 cell counts are associated with improved immune responses to hepatitis B vaccination. New vaccination strategies, such as increased vaccine dose, use of the intradermal route, and addition of adjuvants, could improve response rates in adults with HIV.
•First published vaccine responses in those with monoclonal B cell lymphocytosis (MBL).•High-dose influenza vaccine responses in MBL and chronic lymphocytic leukemia (CLL).•Seroprotection: 63% ...(A/H1N1); 91% (A/H3N2); and 43% (B) for cohort (MBL and CLL).•Higher seroprotection rates for influenza B seen were in those with MBL than CLL.
Limited data are available regarding the immunogenicity of high-dose influenza vaccine among persons with chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL).
A prospective pilot study of humoral immune responses to 2013–2014 and 2014–2015 high-dose trivalent influenza vaccine (HD IIV; Fluzone® High-Dose; Sanofi Pasteur) was conducted among individuals with MBL and previously untreated CLL. Serum hemagglutination inhibition (HAI) antibody titers were measured at baseline and Day 28 after vaccination; seroprotection and seroconversion rates were determined. Memory B cell responses were assessed by B-cell enzyme-linked immune absorbent spotassays.
Thirty subjects (17 CLL and 13 MBL) were included. Median age was 69.5 years. Day 28 seroprotection rates for the cohort were 19/30 (63.3%) for A/H1N1; 21/23 (91.3%) for A/H3N2; and 13/30 (43.3%) for influenza B. Those with MBL achieved higher day 28 HAI geometric mean titers (54.1 4.9, 600.1 vs. 12.1 1.3, 110.1; p = 0.01) and higher Day 28 seroprotection rates (76.9% vs. 17.6%; p = 0.002) against the influenza B-vaccine strain virus than those with CLL.
Immunogenicity of the HD IIV3 in patients with CLL and MBL is lower than reported in healthy adults. Immunogenicity to influenza B was greater in those with MBL than CLL.
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