Use of existing systematic reviews for the development of evidence-based vaccination recommendations: Guidance from the SYSVAC expert panel.

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings

Toll-Like Receptor 2 as a Regulator of Oral Tolerance in the Gastrointestinal Tract

Food allergy, other adverse immune responses to foods, inflammatory bowel disease, and eosinophilic esophagitis have become increasingly common in the last 30 years. It has been proposed in the “hygiene hypothesis” that dysregulated immune responses to environmental microbial stimuli may modify the balance between tolerance and sensitization in some patients. Of the pattern recognition receptors that respond to microbial signals, toll-like receptors (TLRs) represent the most investigated group. The relationship between allergy and TLR activation is currently at the frontier of immunology research. Although TLR2 is abundant in the mucosal environment, little is known about the complex relationship between bystander TLR2 activation by the commensal microflora and the processing of oral antigens. This review focuses on recent advances in our understanding of the relationship between TLR2 and oral tolerance, with an emphasis on regulatory T cells, eosinophils, B cells, IgA, intestinal regulation, and commensal microbes

Toll-Like Receptor 2 as a Regulator of Oral Tolerance in the Gastrointestinal Tract

Food allergy, other adverse immune responses to foods, inflammatory bowel disease, and eosinophilic esophagitis have become increasingly common in the last 30 years. It has been proposed in the "hygiene hypothesis" that dysregulated immune responses to environmental microbial stimuli may modify the balance between tolerance and sensitization in some patients. Of the pattern recognition receptors that respond to microbial signals, toll-like receptors (TLRs) represent the most investigated group. The relationship between allergy and TLR activation is currently at the frontier of immunology research. Although TLR2 is abundant in the mucosal environment, little is known about the complex relationship between bystander TLR2 activation by the commensal microflora and the processing of oral antigens. This review focuses on recent advances in our understanding of the relationship between TLR2 and oral tolerance, with an emphasis on regulatory T cells, eosinophils, B cells, IgA, intestinal regulation, and commensal microbes

Navigating inequities: a roadmap out of the pandemic

The COVID-19 pandemic has exposed social inequities that rival biological inequities in disease exposure and severity. Merely identifying some inequities without understanding all of them can lead to harmful misrepresentations and deepening disparities. Applying an ‘equity lens’ to bring inequities into focus without a vision to extinguish them is short-sighted. Interventions to address inequities should be as diverse as the pluralistic populations experiencing them. We present the first validated equity framework applied to COVID-19 that sheds light on the full spectrum of health inequities, navigates their sources and intersections, and directs ethically just interventions. The Equity Matrix also provides a comprehensive map to guide surveillance and research in order to unveil epidemiological uncertainties of novel diseases like COVID-19, recognising that inequities may exist where evidence is currently insufficient. Successfully applied to vaccines in recent years, this tool has resulted in the development of clear, timely and transparent guidance with positive stakeholder feedback on its comprehensiveness, relevance and appropriateness. Informed by evidence and experience from other vaccine-preventable diseases, this Equity Matrix could be valuable to countries across the social gradient to slow the spread of SARS-CoV-2 by abating the spread of inequities. In the race to SARS-CoV-2 vaccines, this urgently needed roadmap can effectively and efficiently steer global leadership towards equitable allocation with diverse strategies for diverse inequities. Such a roadmap has been absent from discussions on managing the COVID-19 pandemic, and is critical for our passage out of it

IL-7Rα and L-selectin, but not CD103 or CD34, are required for murine peanut-induced anaphylaxis

Background: Allergy to peanuts results in severe anaphylactic responses in affected individuals, and has dramatic effects on society and public policy. Despite the health impacts of peanut-induced anaphylaxis (PIA), relatively little is known about immune mechanisms underlying the disease. Using a mouse model of PIA, we evaluated mice with deletions in four distinct immune molecules (IL7Rα, L-selectin, CD34, CD103), for perturbed responses. Methods: PIA was induced by intragastric sensitization with peanut antigen and cholera toxin adjuvant, followed by intraperitoneal challenge with crude peanut extract (CPE). Disease outcome was assessed by monitoring body temperature, clinical symptoms, and serum histamine levels. Resistant mice were evaluated for total and antigen specific serum IgE, as well as susceptibility to passive systemic anaphylaxis. Results: PIA responses were dramatically reduced in IL7Rα−/− and L-selectin−/− mice, despite normal peanut-specific IgE production and susceptibility to passive systemic anaphylaxis. In contrast, CD34−/− and CD103−/− mice exhibited robust PIA responses, indistinguishable from wild type controls. Conclusions: Loss of L-selectin or IL7Rα function is sufficient to impair PIA, while CD34 or CD103 ablation has no effect on disease severity. More broadly, our findings suggest that future food allergy interventions should focus on disrupting sensitization to food allergens and limiting antigen-specific late-phase responses. Conversely, therapies targeting immune cell migration following antigen challenge are unlikely to have significant benefits, particularly considering the rapid kinetics of PIA.Medicine, Faculty ofNon UBCReviewedFacult

Impact of industry sponsorship on the quality of systematic reviews of vaccines: a cross-sectional analysis of studies published from 2016 to 2019

Background: Systematic reviews (SRs) provide the highest level of evidence and inform evidence-based decision making in health care. Earlier studies found association with industry to be negatively associated with methodological quality of SRs. However, this has not been investigated in SRs on vaccines. Methods: We performed a systematic literature search using MEDLINE and EMBASE in March 2020. The results were restricted to those published between 2016 and 2019 with no language restrictions. Study characteristics were extracted by one person and checked by an experienced reviewer. The methodological quality of the SRs was assessed with the AMSTAR 2 tool by multiple reviewers after a calibration exercise was performed. A summary score for each SR was calculated. The Mann-Whitney U test and Fisher's exact test were performed to compare both groups. Results: Out of 185 SRs that met all inclusion criteria, 27 SRs were industry funded. Those were matched with 30 non-industry funded SRs resulting in a total sample size of 57. The mean AMSTAR 2 summary score across all SRs was 0.49. Overall, the median AMSTAR 2 summary score was higher for the non-industry funded SRs than for the industry-funded SRs (0.62 vs. 0.36; p < .00001). Lower ratings for industry funded SRs were consistent across all but one AMSTAR 2 item, though significantly lower only for three specific items. Conclusion: The methodological quality of SRs in vaccination is comparable to SRs in other fields, while it is still suboptimal. We are not able to provide a satisfactory explanation why industry funded SRs had a lower methodological quality than non-industry funded SRs over recent years. Industry funding is an important indicator of methodological quality for vaccine SRs and should be carefully considered when appraising SR quality

Using existing systematic reviews for developing vaccination recommendations: results of an international expert workshop

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations. Systematic reviews are recommended to be used in this process, but conducting them requires significant resources, which many NITAGs lack. Using existing systematic reviews could help address this problem. The Robert Koch Institute and collaborators set up the SYSVAC2 project to facilitate the retrieval of existing systematic reviews and offer guidance on using them. This will include an online registry of systematic reviews relevant to immunization policy and an online course on how to use existing reviews. This report describes an international expert workshop held in December 2019 to develop consensus on methods for using existing reviews and other relevant factors for the registry and course. Members from NITAGs representing different regions of the world presented their experiences of using systematic reviews and reflected on challenges inhibiting use. Three methodologists considered different aspects of using systematic reviews. Interactive sessions followed, where implications for SYSVAC2 were discussed. Participants supported having critical appraisal ratings, plain language summaries, keyword search, and data visualization functions in the registry. They suggested tailoring course content to different audiences and including overviews of reviews as a topic and examples of how NITAGs have used or could use existing reviews. Participants agreed that whether a review is out-of-date should be decided by those using the review rather than registry staff. The registry could help by highlighting the date of literature search or included primary studies. Participants recommended a visualization function to highlight overlap across reviews and guidance on handling challenges to using reviews, ideally, involving a practical element. No consensus was reached on which critical appraisal tool to use for reviews in the registry, but a majority of participants wanted registry staff to perform appraisals. Formative research is planned before the registry and online course are launched in 2020

Use of existing systematic reviews for the development of evidence-based vaccination recommendations: guidance from the SYSVAC expert panel

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings