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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.

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.

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.sup.+] 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-beta and decreased IFN-y 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., Introduction Before introduction of the pertussis vaccine, about 200,000 cases/year of whooping cough were reported in the US alone (1). A licensed pertussis vaccine that was introduced in the mid-1940s [...]

Author(s): David Sulzer (corresponding author) [1, 2, 3]; Roy N. Alcalay [2]; Francesca Garretti [1]; Lucien Cote [2]; Ellen Kanter [1]; Julian Agin-Liebes [1]; Christopher Liong [2]; Curtis McMurtrey [4]; [...]

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. [ABSTRACT FROM AUTHOR]

Author(s): David Sulzer; Roy N. Alcalay; Francesca Garretti; Lucien Cote; Ellen Kanter; Julian Agin-Liebes; Christopher Liong; Curtis McMurtrey; William H. Hildebrand; Xiaobo Mao; Valina L. Dawson; Ted M. Dawson; Carla [...]

African-Americans in the United States have long since been confronted with harassment and discrimination while traveling because of segregated lodging, restaurants, and other leisure activities. However, African-Americans/Blacks are one of the fastest-growing tourist groups. This work builds on previous research on the Black travel experience analyzing over 300 tweets using the trending hashtag #TravelingWhileBlack through a critical race theory lens. By analyzing how Black tourists are traveling, this study reveals how experiential knowledge of Black travelers can contribute to the learning environment of the tourism industry. Three emergent themes were identified: (1) occurrences of racism, (2) awareness of being Black while traveling, and (3) meaningful experiences traveling while Black, suggesting that experiential knowledge of travelers of color brings different perspectives, which will, it is hoped, move toward eliminating all forms of subordination and create a more just society. [ABSTRACT FROM AUTHOR]