Intra- and Inter-clade Cross-reactivity by HIV-1 Gag Specific T-Cells Reveals Exclusive and Commonly Targeted Regions: Implications for Current Vaccine Trials

The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities

Status of Cardiovascular Disease and Stroke in Hispanics/Latinos in the United States

Background and purposeThis American Heart Association (AHA) scientific statement provides a comprehensive overview of current evidence on the burden cardiovascular disease (CVD) among Hispanics in the United States. Hispanics are the largest minority ethnic group in the United States, and their health is vital to the public health of the nation and to achieving the AHA's 2020 goals. This statement describes the CVD epidemiology and related personal beliefs and the social and health issues of US Hispanics, and it identifies potential prevention and treatment opportunities. The intended audience for this statement includes healthcare professionals, researchers, and policy makers.MethodsWriting group members were nominated by the AHA's Manuscript Oversight Committee and represent a broad range of expertise in relation to Hispanic individuals and CVD. The writers used a general framework outlined by the committee chair to produce a comprehensive literature review that summarizes existing evidence, indicate gaps in current knowledge, and formulate recommendations. Only English-language studies were reviewed, with PubMed/MEDLINE as our primary resource, as well as the Cochrane Library Reviews, Centers for Disease Control and Prevention, and the US Census data as secondary resources. Inductive methods and descriptive studies that focused on CVD outcomes incidence, prevalence, treatment response, and risks were included. Because of the wide scope of these topics, members of the writing committee were responsible for drafting individual sections selected by the chair of the writing committee, and the group chair assembled the complete statement. The conclusions of this statement are the views of the authors and do not necessarily represent the official view of the AHA. All members of the writing group had the opportunity to comment on the initial drafts and approved the final version of this document. The manuscript underwent extensive AHA internal peer review before consideration and approval by the AHA Science Advisory and Coordinating Committee.ResultsThis statement documents the status of knowledge regarding CVD among Hispanics and the sociocultural issues that impact all subgroups of Hispanics with regard to cardiovascular health. In this review, whenever possible, we identify the specific Hispanic subgroups examined to avoid generalizations. We identify specific areas for which current evidence was less robust, as well as inconsistencies and evidence gaps that inform the need for further rigorous and interdisciplinary approaches to increase our understanding of the US Hispanic population and its potential impact on the public health and cardiovascular health of the total US population. We provide recommendations specific to the 9 domains outlined by the chair to support the development of these culturally tailored and targeted approaches.ConclusionsHealthcare professionals and researchers need to consider the impact of culture and ethnicity on health behavior and ultimately health outcomes. There is a need to tailor and develop culturally relevant strategies to engage Hispanics in cardiovascular health promotion and cultivate a larger workforce of healthcare providers, researchers, and allies with the focused goal of improving cardiovascular health and reducing CVD among the US Hispanic population