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In an attempt to move the field of public health from documenting health disparities to acting to rectify them, in 2001, the American Public Health Association (APHA) recognized racism as a fundamental cause of racial health disparities. Both APHA and the Council on Education for Public Health have moved to incorporate new competencies in health equity for public health professionals. As schools and programs of public health work to establish curricular offerings in race and racism, a need exists to identify approaches currently in use that can be replicated, adapted, and scaled. This systematic review sought to identify pedagogical methods and curricula that exist to support the training of US public health students in understanding racism as a structural determinant of health. We found 11 examples from peer-reviewed literature of curricula, lessons, and competencies that have been developed by public health faculty and departments since 2006. The articles discussed a range of approaches to teaching about structural racism in public health, suggesting that little consensus may exist on how to best teach this material. Furthermore, we found little rigorous evaluation of these teaching methods and curricula. The results of this review suggest future research is needed on public health pedagogy on structural racism.

Background Despite significant progress in the field of implementation science (IS), current training programs are inadequate to meet the global need, especially in low-and middle-income countries (LMICs). Even when training opportunities exist, there is a “knowledge-practice gap,” where implementation research findings are not useful to practitioners in a field designed to bridge that gap. This is a critical challenge in LMICs where complex public health issues must be addressed. This paper describes results from a formal assessment of learning needs, priority topics, and delivery methods for LMIC stakeholders. Methods We first reviewed a sample of articles published recently in Implementation Science to identify IS stakeholders and assigned labels and definitions for groups with similar roles. We then employed a multi-step sampling approach and a random sampling strategy to recruit participants (n = 39) for a semi-structured interview that lasted 30–60 min. Stakeholders with inputs critical to developing training curricula were prioritized and selected for interviews. We created memos from audio-recorded interviews and used a deductively created codebook to conduct thematic analysis. We calculated kappa coefficients for each memo and used validation techniques to establish rigor including incorporating feedback from reviewers and member checking. Results Participants included program managers, researchers, and physicians working in over 20 countries, primarily LMICs. The majority had over 10 years of implementation experience but fewer than 5 years of IS experience. Three main themes emerged from the data, pertaining to past experience with IS, future IS training needs, and contextual issues. Most respondents (even with formal training) described their IS knowledge as basic or minimal. Preferences for future training were heterogeneous, but findings suggest that curricula must encompass a broader set of competencies than just IS, include mentorship/apprenticeship, and center the LMIC context. Conclusion While this work is the first systematic assessment of IS learning needs among LMIC stakeholders, findings reflect existing research in that current training opportunities may not meet the demand, trainings are too narrowly focused to meet the heterogeneous needs of stakeholders, and there is a need for a broader set of competencies that moves beyond only IS. Our research also demonstrates the timely and unique needs of developing appropriately scoped, accessible training and mentorship support within LMIC settings. Therefore, we propose the novel approach of intelligent swarming as a solution to help build IS capacity in LMICs through the lens of sustainability and equity.

Human adenovirus serotype 26 (Ad26) is used as a gene-based vaccine against SARS-CoV-2 and HIV-1. Yet, its primary receptor portfolio remains controversial, potentially including sialic acid, CAR, integrins, and CD46. We and others have shown that Ad26 can use CD46, but these observations were questioned by the inability to co-crystallize Ad26 fiber with CD46. Recent work demonstrated that Ad26 binds CD46 with its hexon protein rather than its fiber. We examined the functional consequences of Ad26 for infectionin vitroandin vivo. Ectopic expression of human CD46 on Chinese hamster ovary cells increased Ad26 infection significantly. Deletion of the complement control protein domains CCP1 or CCP2 or the serine-threonine-proline (STP) region of CD46 reduced infection. Comparing wild type and sialic acid-deficient CHO cells, we show that the usage of CD46 is independent of its sialylation status. Ad26 transduction was increased in CD46 transgenic mice after intramuscular (IM) injection, but not after intranasal (IN) administration. Ad26 transduction was 10-fold lower than Ad5 after intratumoral (IT) injection of CD46-expressing tumors. Ad26 transduction of liver was 1000-fold lower than Ad5 after intravenous (IV) injection. These data demonstrate the use of CD46 by Ad26 under certain situations, but also show that the receptor has little consequence by other routes of administration. Finally, IV injection of high doses of Ad26 into CD46 mice induced release of liver enzymes in the bloodstream and reduced white blood cell counts, but did not induce thrombocytopenia. This suggests that Ad26 virions do not induce direct clotting side effects seen during COVID-19 vaccination with this serotype of adenovirus.IMPORTANCEHuman species D Ad26 is being pursued as a low seroprevalence vector for oncolytic virotherapy and gene-based vaccination against HIV-1 and SARS-CoV-2. However, there is debate in the literature about its tropism and receptor utilization, which directly influence its efficiency for certain applications. This work was aimed at determining which receptor(s) this virus uses for infection, and its role in virus biology, vaccine efficacy, and importantly, in vaccine safety.

IntroductionBoth US and global communities lag on key health indicators. There has been limited progress in building capacity to improve health beyond the healthcare field. Yet, communities also need to engage in health improvement initiatives. A substantial body of literature describes standards and core components for quality improvement (QI) approaches in clinical settings. This study aims to determine how communities in the USA, Australia, New Zealand and Canada use QI approaches for health and well-being improvement and how such approaches compare to those in clinical settings.Methods and analysisWe developed a study protocol based on scoping review framework by Arksey and O’Malley, methodological advancements for scoping studies (Levac et al) and other published protocols. We developed research questions in an iterative process and used the Population, Intervention, Comparison, Outcomes strategy to determine eligibility criteria. Electronic databases deemed appropriate (Web of Science, Scopus, and Proquest Health Management) will be searched for studies that meet inclusion criteria. References of included studies will be included when relevant. Two reviewers will independently screen all abstracts and full-text studies for inclusion. A third reviewer will adjudicate disagreements that arise. An instrument will be developed to extract data from included studies. Quantitative and qualitative results will be reported.Ethics and disseminationWe developed this protocol to systematically conduct a scoping review of how US communities use QI approaches to address community health and well-being. Results will benefit multiple stakeholders by informing how to better support, design and evaluate community well-being improvement interventions. Results will be distributed through peer-reviewed journals, conferences, presentations and a public health graduate course.

Our understanding of adenovirus (Ad) biology is largely extrapolated from human species C Ad5. Most humans are immune to Ad5, so lower-seroprevalence viruses like human Ad6 and Ad26 are being tested as therapeutic vectors. Ad6 and Ad26 differ at the DNA level by 34%. To better understand how this might impact their biology, we examined the life cycle of the two viruses in human lung cells in vitro . Both viruses infected A549 cells with similar efficiencies, executed DNA replication with identical kinetics within 12 h, and began killing cells within 72 h. While Ad6-infected cells remained adherent until death, Ad26-infected cells detached within 12 h of infection but remained viable. Next-generation sequencing (NGS) of mRNA from infected cells demonstrated that viral transcripts constituted 1% of cellular mRNAs within 6 h and 8 to 16% within 12 h. Quantitative PCR and NGS revealed the activation of key early genes at 6 h and transition to late gene activation by 12 h by both viruses. There were marked differences in the balance of E1A and E1B activation by the two viruses and in the expression of E3 immune evasion mRNAs. Ad6 was markedly more effective at suppressing major histocompatibility complex class I (MHC I) display on the cell surface and in evading TRAIL-mediated apoptosis than was Ad26. These data demonstrate shared as well as divergent life cycles in these genetically distant human adenoviruses. An understanding of these differences expands the knowledge of alternative Ad species and may inform the selection of related Ads for therapeutic development. IMPORTANCE A burgeoning number of adenoviruses (Ads) are being harnessed as therapeutics, yet the biology of these viruses is generally extrapolated from Ad2 and Ad5. Here, we are the first to compare the transcriptional programs of two genetically distant Ads by mRNA next-generation sequencing (NGS). Species C Ad6 and Ad26 are being pursued as lower-seroprevalence Ad vectors but differ at the DNA level by 34%. Head-to-head comparison in human lung cells by NGS revealed that the two viruses generally conform to our general understanding of the Ad transcriptional program. However, fine mapping revealed subtle and strong differences in how these two viruses execute these programs, including differences in the balance of E1A and E1B mRNAs and in E3 immune evasion genes. This suggests that not all adenoviruses behave like Ad2 and Ad5 and that they may have unique strategies to infect cells and evade the immune system.

The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.

Hepatitis C virus (HCV) infection remains a serious public health problem worldwide. Treatments are limited, and no preventive vaccine is available. Toward developing an HCV vaccine, we engineered two recombinant measles viruses (MVs) expressing structural proteins from the prototypic HCV subtype 1a strain H77. One virus directs the synthesis of the HCV capsid (C) protein and envelope glycoproteins (E1 and E2), which fold properly and form a heterodimer. The other virus expresses the E1 and E2 glycoproteins separately, with each one fused to the cytoplasmic tail of the MV fusion protein. Although these hybrid glycoproteins were transported to the plasma membrane, they were not incorporated into MV particles. Immunization of MV-susceptible, genetically modified mice with either vector induced neutralizing antibodies to MV and HCV. A boost with soluble E2 protein enhanced titers of neutralizing antibody against the homologous HCV envelope. In animals primed with MV expressing properly folded HCV C-E1-E2, boosting also induced cross-neutralizating antibodies against two heterologous HCV strains. These results show that recombinant MVs retain the ability to induce MV-specific humoral immunity while also eliciting HCV neutralizing antibodies, and that anti-HCV immunity can be boosted with a single dose of purified E2 protein. The use of MV vectors could have advantages for pediatric HCV vaccination.