A systematic review on vaccine developmental approaches: Evaluating efficacy, and addressing challenges of infectious diseases in the post-COVID-19 era.

The history of successful vaccination against severe viral diseases such as smallpox poliomyelitis or measles led to the initial hope that a vaccine against AIDS would be developed quickly. However an effective vaccine against HIV needs to overcome substantial obstacles that emerged as research progressed. Due to life cycle HIV can effectively hide from the host immune response integrating itself as proviral DNA in the host cell genome. A strategy pursued to deal with this difficulty is to include early viral regulatory proteins such as Tat Rev or Nef as vaccine antigens for induction of immune responses that can recognize and destroy HIV-infected cells as soon as the virus life cycle is activated [12]. The virus preferentially targets and destroys host immune cells such as T-helper lymphocytes macrophages and dendritic cells that are probably essential to maintain an effective antiviral immune response. This would imply that vaccine-elicited immunity unlikely to be able to prevent infection itself must be able to quickly control virus replication to prevent harm to the immune system. The high antigenic variability of HIV can be considered as an extremely effective immune-evasion strategy. Because of the low fidelity of the viral RNA polymerase virus progeny always represents a collection of RNA genomes (quasi-species) with random mutations. In vivo selection of immunodeficiency virus variants that can evade the recognition of neutralizing antibodies is common and strong virus-specific cytotoxic T-cell responses can select for escape variants already during resolution of primary viremia [3]. Most HIV infections are acquired sexually via the genital or rectal mucosae; however at these entry sites it appears difficult to induce strong antiviral immunity by vaccination. Finally HIV infection is a poverty-related disease that is particularly threatening health in societies of the developing world. Therefore vaccine candidates must be safe and feasible in production and administration to be eligible for use where most needed. (excerpt)

Legal agreements: barriers and enablers to global equitable COVID-19 vaccine access

Meta-analysis is a prominent method for estimating the effects of public health interventions, yet these interventions are often complex in ways that pose challenges to using conventional meta-analytic methods. This article discusses meta-analytic techniques that can be used in research syntheses on the effects of complex public health interventions. We first introduce the use of complexity frameworks to conceptualize public health interventions. We then present a menu of meta-analytic procedures for addressing various sources of complexity when answering questions about the effects of public health interventions in research syntheses. We conclude with a review of important practices and key resources for conducting meta-analyses on complex interventions, as well as future directions for research synthesis more generally. Overall, we argue that it is possible to conduct meaningful quantitative syntheses of research on the effects of public health interventions, though these meta-analyses may require the use of advanced techniques to properly consider and attend to issues of complexity.

Fluoridation of community water supplies constitutes one of the most effective public health interventions for preventing dental caries. In recent years, questions have been raised about its effectiveness and safety. This study aims to systematically review and summarize the existing evidence on community water fluoridation (CWF) and dental caries in permanent and deciduous teeth. Five databases and 3 gray databases were searched for relevant studies. Paired reviewers independently screened the studies, extracted data, and assessed their methodological quality. Standard mean differences (SMDs) for dmf(s)/DMFT(S) (decayed, missing, and filled teeth/surface) and odds ratios (ORs) for caries prevalence were measured between exposure or not to CFW for deciduous and permanent teeth. Subgroup analysis was performed to explore whether the study design, continent, or decade of publication changed the point estimates. Seventy-four studies were included in the qualitative analysis: 57 cross-sectional, 13 before-and-after, and 4 cohort studies. Thirty-two studies provided sufficient data for meta-analyses. The overall SMD of DMFT and dmf in those exposed to CWF compared with unexposed were -0.32 (95% confidence interval [CI]: -0.48 to -0.17, I2 = 96%, P < 0.01) and -0.30 (95% CI: -0.39 to -0.21, I2 = 88%, P < 0.01), respectively. The prevalence of caries was smaller in those exposed to CWF for both the permanent (OR = 0.52, 95% CI: 0.43 to 0.63) and deciduous (OR = 0.60, 95% CI: 0.48 to 0.76) dentitions. Study design, continent, or decade of publication satisfactorily explained the heterogeneity between studies. Communities where water was fluoridated experienced less caries and differences expressed in terms of SMD and prevalence (OR) where of high magnitude, both in children and in adults. The results of the meta-analyses revealed significant differences in caries experience and prevalence in favor of CWF, which represents an effective and comprehensive public health intervention for caries prevention, especially in the primary dentition.Knowledge Transfer Statement:Based on the published literature, the results of this study show that fluoridation of community water supplies is still an effective public health intervention to prevent dental caries, both in children and adults, despite the widespread availability of fluoride-containing dental products, especially toothpaste. This result adds to the existing evidence to support its incorporation into public oral health policies.

Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss

Intracellular trafficking and transgene expression of viral and non-viral gene vectors

CNS-targeted Viral Delivery of G-CSF in an Animal Model for ALS: Improved Efficacy and Preservation of the Neuromuscular Unit

Cell and gene: from transduction to translation

Report to Congress: Social Risk Factors and Performance Under Medicare’s Value-based Purchasing Programs.1 US Department of Health and Human Services, Office of the Assistant Secretary for Planning and Evaluation. December 21, 2016. ### Policy Context Value-based purchasing (VBP), or pay-for-performance, comprises a growing portion of Medicare payment and the changes in physician payment enacted in the Medicare and Children's Health Insurance Program Reauthorization Act are likely to accelerate these trends even further.2 Simultaneously, there is growing consensus that social risk factors—such as income, race and ethnicity, and community environment—play a major role in health.3–5 Persistent and meaningful gaps exist in health and even in life expectancy based on these factors.6–9 These 2 issues intersect in VBP. If beneficiaries with social risk factors have worse health outcomes because of factors beyond providers’ control, providers could be unfairly disadvantaged under VBP. On the contrary, if beneficiaries with social risk factors have worse health outcomes because the providers serving them provide low-quality care, the financial incentives and accountability of VBP could be an important strategy for improving care and reducing disparities. In 2014, Congress passed the Improving Medicare Postacute Care Transformation Act (IMPACT),10 which required that the Office of the Assistant Secretary for Planning and Evaluation (ASPE) at the US Department of Health and Human Services complete an empirical report addressing the issue of social risk in Medicare’s current VBP programs to assist Congress in further decision making on this issue. The report covered here is the first component of the required work, which was submitted to Congress in December 2016. The ASPE report may have particular salience to cardiovascular clinicians, who practice every day in an environment significantly impacted by VBP. Many current quality measures in inpatient and outpatient VBP programs are cardiovascular in nature; patients …

Maintaining Warp Speed: Policy Requirements for a Just-in-Time, Capability-Based, Scalable Medical Countermeasure Research and Development Enterprise.

<h3>Abstract</h3> Gene therapy is the most promising strategy for treating a number of diseases at their most fundamental, genetic level, and it has a wide range of promising clinical and...

Building a hybrid virtual cardiac rehabilitation program to promote health equity: Lessons learned

Nucleic acids (NA) therapies, including therapy with genes, aptamers or antisense oligonucleotides, have been showing promising results, especially in the treatment of severe diseases (e.g. cancer and AIDS). Nevertheless, the full success of medical treatments requires efficient achievement of the therapeutic target and also the safety and effectiveness of the pharmaceutical system. NA are not very efficient when administered alone, which means that the use of appropriate methods for in vivo transfection of these molecules into targeted cells is fundamental. Examples of these techniques are the use of viral and non-viral vectors to transfer the NA to the cells nucleus. Despite viral vectors have been demonstrating superior effectiveness for NA transfer, some drawbacks have been pointed out, which focused the research in the non-viral vectors. However, the development of effective NA delivery systems remains a challenge for pharmaceutical technologists, mainly because of their in vivo failure, which hinders their clinical application. In this review article we address the characteristics of NA molecules and their respective limitations for formulation and administration. An update on the state of the art related to the latest and outstanding developments from the in vivo applications of NA viral and non-viral delivery systems is also presented. From this review, we can conclude that there is a lack of research regarding pre-clinical studies in specific animal models of disease, which is required for further human clinical trials and for their use in clinics.

Vaccines represent the most relevant contribution of immunology to human health. However, despite the remarkable success achieved in the past years, many vaccines are still missing in order to fight important human pathologies and to prevent emerging and re-emerging diseases. For these pathogens the known strategies for making vaccines have been unsuccessful and thus, new avenues should be investigated to overcome the failure of clinical trials and other important issues including safety concerns related to live vaccines or viral vectors, the weak immunogenicity of subunit vaccines and side effects associated with the use of adjuvants. A major hurdle of developing successful and effective vaccines is to design antigen delivery systems in such a way that optimizes antigen presentation and induces broad protective immune responses. Recent advances in vector delivery technologies, immunology, vaccinology and system biology, have led to a deeper understanding of the molecular and cellular mechanisms by which vaccines should stimulate both arms of the adaptive immune responses, offering new strategies of vaccinations. This review is an update of current strategies with respect to live attenuated and inactivated vaccines, DNA vaccines, viral vectors, lipid-based carrier systems such as liposomes and virosomes as well as polymeric nanoparticle vaccines and virus-like particles. In addition, this article will describe our work on a versatile and immunogenic delivery system which we have studied in the past decade and which is derived from a non-pathogenic prokaryotic organism: the "E2 scaffold" of the pyruvate dehydrogenase complex from Geobacillus stearothermophilus.

Adeno-Associated Virus Vectors in Clinical Trials