Barriers to and facilitators of hormonal and long-acting reversible contraception access and use in the US among reproductive-aged women who use opioids: A scoping review.

Existing research has found that women who use opioids (WWUO) experience challenges to hormonal and long-acting reversible contraception (HC-LARC) access and use. Facilitators of such use are unclear. We conducted a scoping review to comprehensively map the literature on barriers to and facilitators of HC-LARC access and use in the United States among reproductive-aged WWUO. In accordance with the JBI Manual of Evidence Synthesis, we conducted literature searches for empirical articles published from 1990 to 2021. Independent reviewers screened references, first by titles and abstracts, then by full-text, and charted data of eligible articles. We coded and organized HC-LARC barriers and facilitators according to a four-level social-ecological model (SEM) and categorized findings within each SEM level into domains. We screened 4,617 records, of which 28 articles focusing on HC-LARC (n = 18), LARC only (n = 6), or testing an intervention to increase HC-LARC uptake (n = 4) met inclusion criteria. We identified 13 domains of barriers and 11 domains of facilitators across four SEM levels (individual, relationship, community, societal). The most frequently cited barriers and facilitators were methods characteristics, partner and provider relations, transportation, healthcare availability and accessibility, cost, insurance, and stigma. Future studies would benefit from recruiting participants and collecting data in community settings, targeting more diverse populations, and identifying neighborhood, social, and policy barriers and facilitators. Reducing barriers and improving equity in HC-LARC access and use among WWUO is a complex, multifaceted issue that will require targeting factors simultaneously at multiple levels of the social-ecological hierarchy to effect change.

Generation of Norovirus-Specific T Cells From Human Donors With Extensive Cross-Reactivity to Variant Sequences: Implications for Immunotherapy.

BACKGROUND: Chronic norovirus infection in immunocompromised patients can be severe, and presently there is no effective treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the treatment of many viral infections, and this could represent a novel treatment approach for chronic norovirus infection. Hence, we sought to generate human norovirus-specific T cells (NSTs) that can recognize different viral sequences. METHODS: Norovirus-specific T cells were generated from peripheral blood of healthy donors by stimulation with overlapping peptide libraries spanning the entire coding sequence of the norovirus genome. RESULTS: We successfully generated T cells targeting multiple norovirus antigens with a mean 4.2 ± 0.5-fold expansion after 10 days. Norovirus-specific T cells comprised both CD4+ and CD8+ T cells that expressed markers for central memory and effector memory phenotype with minimal expression of coinhibitory molecules, and they were polyfunctional based on cytokine production. We identified novel CD4- and CD8-restricted immunodominant epitopes within NS6 and VP1 antigens. Furthermore, NSTs showed a high degree of cross-reactivity to multiple variant epitopes from clinical isolates. CONCLUSIONS: Our findings identify immunodominant human norovirus T-cell epitopes and demonstrate that it is feasible to generate potent NSTs from third-party donors for use in antiviral immunotherapy.

Generation of Zika virus-specific T cells from seropositive and virus-naïve donors for potential use as an autologous or "off-the-shelf" immunotherapeutic.

BACKGROUND: Zika virus (ZIKV) infection can cause severe birth defects in newborns with no effective currently available treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the prevention or treatment of many viral infections, and could represent a novel treatment approach for patients with ZIKV infection. However, extending this strategy to the ZIKV setting has been hampered by limited data on immunogenic T-cell antigens within ZIKV. Hence, we have generated ZIKV-specific T cells and characterized the cellular immune responses against ZIKV antigens. METHODS: T-cell products were generated from peripheral blood of ZIKV-exposed donors, ZIKV-naive adult donors and umbilical cord blood by stimulation with pentadecamer (15mer) overlapping peptide libraries spanning four ZIKV polyproteins (C, M, E and NS1) using a Good Manufacturing Practice-compliant protocol. RESULTS: We successfully generated T cells targeting ZIKV antigens with clinically relevant numbers. The ex vivo-expanded T cells comprised both CD4+ and CD8+ T cells that were able to produce Th1-polarized effector cytokines and kill ZIKV-infected HLA-matched monocytes, confirming functionality of this unique T-cell product as a potential "off-the-shelf" therapeutic. Epitope mapping using peptide arrays identified several novel HLA class I and class II-restricted epitopes within NS1 antigen, which is essential for viral replication and immune evasion. DISCUSSION: Our findings demonstrate that it is feasible to generate potent ZIKV-specific T cells from a variety of cell sources including virus naïve donors for future clinical use in an "off-the-shelf" setting.