T cells from patients with Parkinson's disease recognize α-synuclein peptides.

Genetic studies have shown the association of Parkinson's disease with alleles of the major histocompatibility complex. Here we show that a defined set of peptides that are derived from α-synuclein, a protein aggregated in Parkinson's disease, act as antigenic epitopes displayed by these alleles and drive helper and cytotoxic T cell responses in patients with Parkinson's disease. These responses may explain the association of Parkinson's disease with specific major histocompatibility complex alleles.

Erratum: T cells from patients with Parkinson's disease recognize α-synuclein peptides.

This corrects the article DOI: 10.1038/nature22815.

Widespread Tau-Specific CD4 T Cell Reactivity in the General Population.

Tau protein is found to be aggregated and hyperphosphorylated (p-tau) in many neurologic disorders, including Parkinson disease (PD) and related parkinsonisms, Alzheimer disease, traumatic brain injury, and even in normal aging. Although not known to produce autoimmune responses, we hypothesized that the appearance of aggregated tau and p-tau with disease could activate the immune system. We thus compared T cell responses to tau and p-tau-derived peptides between PD patients, age-matched healthy controls, and young healthy controls (<35 y old; who are less likely to have high levels of tau aggregates). All groups exhibited CD4+ T cell responses to tau-derived peptides, which were associated with secretion of IFN-γ, IL-5, and/or IL-4. The PD and control participants exhibited a similar magnitude and breadth of responses. Some tau-derived epitopes, consisting of both unmodified and p-tau residues, were more highly represented in PD participants. These results were verified in an independent set of PD and control donors (either age-matched or young controls). Thus, T cells recognizing tau epitopes escape central and peripheral tolerance in relatively high numbers, and the magnitude and nature of these responses are not modulated by age or PD disease.

A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans.

We performed a quantitative analysis of the HLA restriction, antigen and epitope specificity of human pathogen specific responses in healthy individuals infected with M. tuberculosis (Mtb), in a South African cohort as a test case. The results estimate the breadth of T cell responses for the first time in the context of an infection and human population setting. We determined the epitope repertoire of eleven representative Mtb antigens and a large panel of previously defined Mtb epitopes. We estimated that our analytic methods detected 50-75% of the total response in a cohort of 63 individuals. As expected, responses were highly heterogeneous, with responses to a total of 125 epitopes detected. The 66 top epitopes provided 80% coverage of the responses identified in our study. Using a panel of 48 HLA class II-transfected antigen-presenting cells, we determined HLA class II restrictions for 278 epitope/donor recognition events (36% of the total). The majority of epitopes were restricted by multiple HLA alleles, and 380 different epitope/HLA combinations comprised less than 30% of the estimated Mtb-specific response. Our results underline the complexity of human T cell responses at a population level. Efforts to capture and characterize this broad and highly HLA promiscuous Mtb-specific T cell epitope repertoire will require significant peptide multiplexing efforts. We show that a comprehensive "megapool" of Mtb peptides captured a large fraction of the Mtb-specific T cells and can be used to characterize this response.

Differential Recognition of Mycobacterium tuberculosis-Specific Epitopes as a Function of Tuberculosis Disease History.

RATIONALE: Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVES: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. METHODS: T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. MEASUREMENTS AND MAIN RESULTS: We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. CONCLUSIONS: Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.

Identification of minimum thresholds for dietary self-monitoring to promote weight-loss maintenance.

OBJECTIVE: Reduced schedules of dietary self-monitoring are typically recommended after the end of behavioral weight-loss programs; however, there exists little empirical evidence to guide these recommendations. METHODS: We explored potential thresholds for dietary self-monitoring during a 9-month maintenance period following a 3-month weight-loss program in 74 adults with overweight or obesity (mean [SD] age = 50.7 [10.4] years, BMI = 31.2 [4.5] kg/m2) who were encouraged to self-monitor weight, dietary intake, and physical activity daily and report their adherence to self-monitoring each week via a study website. RESULTS: Greater self-monitoring was correlated with less weight regain for thresholds of ≥3 days/week, with the largest benefit observed for thresholds of ≥5 to ≥6 days/week (all p < 0.05); significant weight gain was observed for thresholds of ≥1 to ≥2 days/week, whereas no change in weight was observed for thresholds of ≥3 to ≥4 days/week, and weight loss was observed with thresholds of ≥5 or more days/week. CONCLUSIONS: Results demonstrate that self-monitoring at least 3 days/week may be beneficial for supporting long-term maintenance, although greater benefit (in relation to weight loss) may be realized at thresholds of 5 to 6 days/week. Future research should investigate whether individuals who were randomized to self-monitor at these different thresholds demonstrate differential patterns of weight-loss maintenance.

Hunger, temptation, and dietary adherence during weight management.

Preliminary evidence suggests that hunger and temptation may predict nonadherence to dietary intake goals; however, no studies have investigated the potential interaction between hunger and temptation in relation to dietary nonadherence nor have any investigated whether these associations may be different after the end of active behavioral intervention. Thus, the current study examined the week-to-week associations between hunger, temptation, and dietary adherence in 74 adults with overweight or obesity (mean ± SD age = 50.7 ± 10.4, BMI = 31.2 ± 4.5 kg/m2) enrolled in a 12-week, Internet-based weight loss program followed by a 40-week post-intervention observational maintenance period. Each week during the study, participants completed a questionnaire on which they rated their hunger, temptation, and dietary adherence on 7-point scales. Multilevel models demonstrated that higher levels of hunger and temptation were associated with lower ratings of dietary adherence during the same week, ps < 0.0001, such that 1-point higher ratings of hunger or temptation were associated with 0.2- and 0.5-point lower ratings of dietary adherence, respectively. Further, there was an interaction between hunger and temptation such that the association between temptation and dietary nonadherence was stronger when ratings of hunger were lower, p = .028. There were no differences in associations between the initial weight loss period and the maintenance period. Results suggest that hunger and temptation may serve as potential treatment targets for interventions aimed at improving adherence to dietary intake goals. Future studies should investigate whether interventions targeting hunger and temptation can improve dietary adherence and weight loss outcomes.

Consistency With and Disengagement From Self-monitoring of Weight, Dietary Intake, and Physical Activity in a Technology-Based Weight Loss Program: Exploratory Study.

BACKGROUND: Digital self-monitoring tools offer promise to improve adherence to self-monitoring of weight and weight-related behaviors; however, less is known regarding the patterns of participant consistency and disengagement with these tools. OBJECTIVE: This study characterizes the consistency of use and time to disengagement with digital self-monitoring tools during a 6-month weight loss intervention and investigates whether the provision of phone-based intervention improved self-monitoring adherence. METHODS: Participants were 54 adults with overweight or obesity (mean age 49.6 years, SD 12.4 years; mean BMI 32.6 kg/m2, SD 3.2 kg/m2) enrolled in a pilot trial assessing the impact of self-monitoring technology (Fitbit Zip, Aria scale, and smartphone app), with and without additional interventionist contact, on weight loss. All participants received weight loss education and were asked to self-monitor weight, dietary intake, and physical activity daily throughout the 6-month program. Consistency was defined as the number of weeks that participants adhered to self-monitoring recommendations (7 out of 7 days). Disengagement was defined as the first of 2 consecutive weeks that the 7-day self-monitoring adherence goal was not met. Wilcoxon signed-rank tests were used to examine differences in consistency and disengagement by behavioral targets. t tests (2-tailed) and Cox proportional hazards models were used to examine whether providing additional interventionist contact would lead to significant improvements in consistency and time to disengagement from self-monitoring tools, respectively. Linear regressions were used to examine associations between consistency, time to disengagement, and weight loss. RESULTS: Participants consistently self-monitored physical activity for more weeks (mean 17.4 weeks, SD 8.5 weeks) than weight (mean 11.1 weeks, SD 8.5 weeks) or dietary intake (mean 10.8 weeks, SD 8.7 weeks; P<.05). Similarly, participants had a significantly longer time to disengagement from self-monitoring of physical activity (median 19.5 weeks) than weight (4 weeks) or dietary intake (10 weeks; P<.001). Participants randomized to receive additional interventionist contact had significantly greater consistency and longer time to disengagement for self-monitoring of dietary intake compared with participants who did not (P=.006); however, there were no statistically significant differences between groups for self-monitoring of weight or physical activity (P=.24 and P=.25, respectively). Greater consistency and longer time to disengagement were associated with greater weight loss for self-monitoring of weight and dietary intake (P<.001 and P=.004, respectively) but not for physical activity (P=.57). CONCLUSIONS: Results demonstrated that self-monitoring adherence differed by behavioral target, with greater consistency and longer time to disengagement associated with lower-burden tools (ie, self-monitoring of physical activity). Consistent with supportive accountability theory, additional interventionist contact improved consistency and lengthened time to disengagement from self-monitoring of dietary intake. Given the observed associations between consistency, disengagement, and weight loss outcomes, it is important to identify additional methods of increasing consistency and engagement with digital self-monitoring tools.

Using self-monitoring technology for nutritional counseling and weight management.

Self-monitoring of weight, dietary intake, and physical activity is a key strategy for weight management in adults with obesity. Despite research suggesting consistent associations between more frequent self-monitoring and greater success with weight regulation, adherence is often suboptimal and tends to decrease over time. New technologies such as smartphone applications, e-scales, and wearable devices can help eliminate some of the barriers individuals experience with traditional self-monitoring tools, and research has demonstrated that these tools may improve self-monitoring adherence. To improve the integration of these tools in clinical practice, the current narrative review introduces the various types of self-monitoring technologies, presents current evidence regarding their use for nutrition support and weight management, and provides guidance for optimal implementation. The review ends with a discussion of barriers to the implementation of these technologies and the role that they should optimally play in nutritional counseling and weight management. Although newer self-monitoring technologies may help improve adherence to self-monitoring, these tools should not be viewed as an intervention in and of themselves and are most efficacious when implemented with ongoing clinical support.

Awareness, Acceptability, and Perceived Effectiveness of Text-Based Therapy Among Graduate Students: Cross-sectional Study.

BACKGROUND: Research has suggested that there is a mental health crisis occurring among graduate students in the United States. Moreover, many students go without effective treatment owing to the limited availability of mental and behavioral health resources on college campuses. Text-based therapy may represent a viable method for increasing access to mental health support for graduate students, but little is known regarding its acceptability in this population. OBJECTIVE: The purpose of this study was to assess how graduate students perceive text-based therapy and their likelihood of seeking out this form of therapy. METHODS: In total, 265 graduate students completed a cross-sectional web-based survey that included multiple-choice and open-ended questions assessing their perceptions of text-based therapy and the likelihood of seeking out this form of therapy. Chi-square tests, ANOVAs, and nonparametric Wilcoxon signed-rank tests were used to examine differences in multiple-choice questions. The constant comparative method was used for qualitative analyses of the open-ended question responses. RESULTS: Participants (n=265) were predominately non-Hispanic White (166/265, 62.6%) and female (167/265, 63%) with a mean age of 28.3 (SD 5.1) years. Over half of the participants (139/265, 52.5%) were not aware that text-based therapy existed; however, 65.3% (173/265) reported that they would consider using text-based services, if available. In comparison to face-to-face therapy, participants reported being less likely to seek out text-based therapy and perceived it as less effective (P<.001). Qualitative results indicated that participants were concerned about the ability to effectively communicate and build rapport through text-based therapy and thought that this modality may be more effective for some mental and behavioral health concerns than others. Moreover, participants noted that text-based therapy would be best implemented as a way to supplement, rather than replace, face-to-face services. CONCLUSIONS: Altogether, the results of this study suggest that text-based therapy holds the potential to increase access to and use of mental and behavioral health services; however, graduate students remain concerned about its effectiveness and the optimal methods of implementation. Future research should investigate how therapeutic processes (eg, effective communication and rapport-building) can be facilitated in digital environments and how text-based therapy could be best implemented to supplement and extend, rather than replace, face-to-face services.

Impact of transition from face-to-face to telehealth on behavioral obesity treatment during the COVID-19 pandemic.

OBJECTIVE: This study evaluated whether the transition of a face-to-face behavioral intervention to videoconferencing-based telehealth delivery during the COVID-19 pandemic resulted in significantly smaller weight losses than those typically observed in gold-standard, face-to-face programs. METHODS: Participants were 160 adults with obesity (mean [SD] age = 49.2 [11.9] years, BMI = 36.1 [4.2] kg/m2 ) enrolled in two cohorts of a 16-week comprehensive weight-management program. Cohort 1 began in person and transitioned to telehealth (Zoom) delivery during week 11 of the intervention because of COVID-19; Cohort 2 was conducted completely remotely. A noninferiority approach (using a clinically relevant noninferiority margin of 2.5%) was used to assess whether the weight losses observed were inferior to the 8% losses from baseline typically produced by gold-standard, face-to-face lifestyle interventions. RESULTS: From baseline to postintervention, participants lost an average of 7.4 [4.9] kg, representing a reduction of 7.2% [4.6%]. This magnitude of weight change was significantly greater than 5.5% (t[159] = 4.7, p < 0.001), and, thus, was within the proposed noninferiority margin. CONCLUSIONS: These findings demonstrate that the results of behavioral weight-management interventions are robust, whether delivered in person or remotely, and that individuals can achieve clinically meaningful benefits from behavioral treatment even during a global pandemic. Pragmatic "lessons learned," including modified trial recruitment techniques, are discussed.

Randomized controlled trial of financial incentives during weight-loss induction and maintenance in online group weight control.

OBJECTIVE: This study examined the impact of a financial incentive scheme integrating process and outcome incentives across weight-loss induction and weight maintenance on 18-month weight outcomes. METHODS: This was a randomized controlled trial. Participants with overweight or obesity (n = 418; 91% female; 28% racial/ethnic minority) were randomized to an 18-month, online, group-based behavioral weight-control program (Internet-Only) or the same program with financial incentives provided for 12 months, contingent on self-regulatory weight-control behaviors (self-weighing, dietary self-monitoring, and physical activity) and weight-outcome benchmarks (Internet+Incentives). No financial incentives were provided from Months 13 to 18 to examine the durability of weight-control behaviors and outcomes without incentives. RESULTS: Weight-loss induction at Month 6 was significantly greater for Internet+Incentives than Internet-Only (6.8% vs. 4.9%, respectively, p = 0.01). Individuals receiving incentives were significantly more likely to maintain weight loss ≥ 5% at Month 12 (45% in Internet+Incentives vs. 32% in Internet-Only, p < 0.02) and remain weight stable (39% vs. 27%, respectively, p < 0.01). Internet+Incentives participants also reported significantly greater behavioral engagement through Month 12. However, once incentives ceased, there were no differences in sustained weight outcomes (Month 18), and engagement declined dramatically. CONCLUSIONS: Despite promoting greater treatment engagement and initial weight loss, financial incentives as offered in this study did not promote better extended weight control.

A Comparison of Sedentary Behavior as Measured by the Fitbit and ActivPAL in College Students.

Previous studies have examined the ability of the Fitbit to measure physical activity compared to research-grade accelerometers. However, few have examined whether Fitbits accurately measure sedentary behavior. This study examined whether the Fitbit Charge 3 adequately quantifies sedentary behavior compared to the gold standard in objectively measured sedentary behavior assessment, the activPAL. Eleven adults wore a Fitbit Charge 3 and activPAL device for 14 days and self-reported their sedentary behavior each week. ActivPAL epoch data were summed into minute-by-minute data and processed with two cutpoints (activPAL_Half and activPAL_Full) to compare to Fitbit data. Paired t-tests were used to examine differences between the two devices for sedentary behavior variables. Intraclass correlations were used to examine device agreement. There was no significant difference in sedentary time between activPAL_Half and Fitbit data, but activPAL_Full estimated significantly lower sedentary time than Fitbit. Intraclass correlations showed high agreement. We suggest that Fitbit could replace activPAL when measuring total sedentary time.

An Exploration of Domain-Specific Sedentary Behaviors in College Students by Lifestyle Factors and Sociodemographics.

College students exhibit high levels of sedentary time and/or poor lifestyle factors (e.g., poor sleep, stress, physical inactivity). It is unknown; however, in what domains college students spend their sedentary time and whether there are associations between sedentary time and these lifestyle factors. This study examined sedentary behavior of college students by domains, current lifestyle factors and sociodemographics. Undergraduates (n = 272, M age = 20 years, 79% female) self-reported their sedentary behavior, sleep, stress, physical activity, anthropometrics and sociodemographics. Sedentary time was categorized as: total, recreational screen, education and social. Students reported spending > 12 h of their day sedentary on average, with over a third of this time spent in recreational screen time. All categories of sedentary time were significantly correlated with body mass index, and both total sedentary time and screen time were significantly correlated with sleep score, with poorer sleep quality associated with greater sedentary time. Physical activity was negatively correlated with social sedentary time only. Subgroups with elevated sedentary time included minority students, those with low parental education and students with overweight/obesity. Given the negative health impacts of sedentary behavior, college students would likely benefit from interventions tailored to this population which target reducing sedentary time, particularly recreational screen time.

Weight Status and Sedentary Behavior of Alzheimer's Disease Caregivers.

Objectives: In this study, we sought to characterize the weight status, sedentary behavior, and physical activity of caregivers of individuals with Alzheimer's disease. Methods: In 2014, we surveyed caregivers of individuals with Alzheimer's disease from the South Carolina Alzheimer's Disease Registry (N = 47) about their personal health behaviors. Additionally, a subset of individuals (N = 14) wore an accelerometer for 7 days. Results: Caregivers (N = 47) were mostly overweight or obese (85%) and self-reported a daily average sedentary time of 246.5 ± 203.0 minutes and 455.8 ± 291.4 minutes, as measured by 2 questionnaires. Objective measures indicated that persons spent an average of 769.4 ± 167.6 minutes per day (77.8% of their waking day) engaged in sedentary behavior. Conclusion: Given the negative health outcomes associated with both obesity and sedentary behavior, this is a vulnerable population that likely would benefit from interventions focused on weight management and reducing sedentary behavior.

Adding Financial Incentives to Online Group-Based Behavioral Weight Control: An RCT.

INTRODUCTION: Internet-delivered behavioral weight control is promising for expanding the reach and availability of weight management, but online programs produce lower weight losses than typically achieved in person. Financial incentives have been shown to increase weight losses. This study examined whether adding financial incentives for self-monitoring and achieving target weight losses increases weight losses attained in a fully online, group-based behavioral weight management program compared with the same program alone. STUDY DESIGN: This study was an RCT. SETTING/PARTICIPANTS: Adults with overweight and obesity (n=418; 91% female; 28% minority) were recruited from 2 clinical centers. INTERVENTION: The intervention was a 24-session online group-based behavioral weight control program with weekly synchronous chat sessions (Internet-only) or the same program with weekly financial incentives for self-monitoring body weight and dietary intake daily and for achieving target weight losses at 2 and 6 months (Internet + incentives). MAIN OUTCOME MEASURES: This study measured weight loss at 6 months and treatment engagement (attendance, self-monitoring of body weight, dietary intake, and physical activity). Data were collected between February 2016 and August 2018, and analyses were completed in 2019. RESULTS: Participants randomized to the Internet + incentives group lost more weight (-6.4 [SD=5.5] kg) than those in the Internet-only group (-4.7 [SD=6.6] kg; p<0.01). Further, a higher proportion of the Internet + incentives group achieved ≥5% weight loss (55%) than those in the Internet-only group (40%; p<0.05). Treatment engagement was higher in the Internet + incentives condition, with greater self-monitoring of behaviors targeted by incentives, as well as higher rates of behaviors not targeted and higher self-reported physical activity. Study retention was higher among those in the Internet + incentives condition (91%) than those in the Internet-only condition (81%; p=0.003). CONCLUSIONS: Adding financial incentives to a program delivered fully online increases weight losses compared with the program alone and can achieve weight losses comparable to in-person programs, offering potential for substantial geographic reach. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov NCT02688621.

Sequence-based HLA-A, B, C, DP, DQ, and DR typing of 159 individuals from the Worcester region of the Western Cape province of South Africa.

DNA sequence-based typing at the HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, -DRB1, and -DRB3/4/5 loci was performed on samples provided by 159 individuals from the Worcester region of the Western Cape province of South Africa. The purpose of the study was to characterize allele frequencies in the local population, to support studies of T cell immunity against pathogens, including Mycobacterium tuberculosis. There are no detectable deviations from Hardy Weinberg proportions for the HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, and -DRB1 loci. A minor deviation was detected at the HLA-DQB1 locus due to an excess of homozygotes. The genotype data are available in the Allele Frequencies Net Database under identifier 3425.

Microbiota epitope similarity either dampens or enhances the immunogenicity of disease-associated antigenic epitopes.

The microbiome influences adaptive immunity and molecular mimicry influences T cell reactivity. Here, we evaluated whether the sequence similarity of various antigens to the microbiota dampens or increases immunogenicity of T cell epitopes. Sets of epitopes and control sequences derived from 38 antigenic categories (infectious pathogens, allergens, autoantigens) were retrieved from the Immune Epitope Database (IEDB). Their similarity to microbiome sequences was calculated using the BLOSUM62 matrix. We found that sequence similarity was associated with either dampened (tolerogenic; e.g. most allergens) or increased (inflammatory; e.g. Dengue and West Nile viruses) likelihood of a peptide being immunogenic as a function of epitope source category. Ten-fold cross-validation and validation using sets of manually curated epitopes and non-epitopes derived from allergens were used to confirm these initial observations. Furthermore, the genus from which the microbiome homologous sequences were derived influenced whether a tolerogenic versus inflammatory modulatory effect was observed, with Fusobacterium most associated with inflammatory influences and Bacteroides most associated with tolerogenic influences. We validated these effects using PBMCs stimulated with various sets of microbiome peptides. "Tolerogenic" microbiome peptides elicited IL-10 production, "inflammatory" peptides elicited mixed IL-10/IFNγ production, while microbiome epitopes homologous to self were completely unreactive for both cytokines. We also tested the sequence similarity of cockroach epitopes to specific microbiome sequences derived from households of cockroach allergic individuals and non-allergic controls. Microbiomes from cockroach allergic households were less likely to contain sequences homologous to previously defined cockroach allergens. These results are compatible with the hypothesis that microbiome sequences may contribute to the tolerization of T cells for allergen epitopes, and lack of these sequences might conversely be associated with increased likelihood of T cell reactivity against the cockroach epitopes. Taken together this study suggests that microbiome sequence similarity influences immune reactivity to homologous epitopes encoded by pathogens, allergens and auto-antigens.

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters.

In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-ß and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.

A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents.

We compared T cell recognition of 59 prevalently recognized Mycobacterium tuberculosis (MTB) antigens in individuals latently infected with MTB (LTBI), and uninfected individuals with previous BCG vaccination, from nine locations and populations with different HLA distribution, MTB exposure rates, and standards of TB care. This comparison revealed similar response magnitudes in diverse LTBI and BCG-vaccinated cohorts and significant correlation between responses in LTBIs from the USA and other locations. Many antigens were uniformly recognized, suggesting suitability for inclusion in vaccines targeting diverse populations. Several antigens were similarly immunodominant in LTBI and BCG cohorts, suggesting applicability for vaccines aimed at boosting BCG responses. The panel of MTB antigens will be valuable for characterizing MTB-specific CD4 T cell responses irrespective of ethnicity, infecting MTB strains and BCG vaccination status. Our results illustrate how a comparative analysis can provide insight into the relative immunogenicity of existing and novel vaccine candidates in LTBIs.