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PARVAX is a genetic vaccine platform based on an adeno-associated vector that has demonstrated to elicit potent, durable, and protective immunity in nonhuman primates (NHPs) after a single dose. Here, we assessed vaccine immunogenicity following a PARVAX prime-boost regimen against SARS-CoV-2. In mice, a low-dose prime followed by a higher-dose boost elicited potent neutralizing antibody responses and distinct cross-reactivity profiles, depending on the antigen used in the booster vaccine. However, the potent neutralizing anti-vector antibody responses developed in mice limited the dose that could be administered as a prime. We further explored the re-administration efficacy in NHPs primed with a SARS-CoV-2 Delta vaccine and boosted with an Omicron BA.1 vaccine at week 15, after the primary response peak antibody levels were reached. The boost elicited an increase in antibodies against several Omicron variants, but no increase was detected in the antibody titers for other variants. The anti-vector responses were low and showed some increased subsequent boosts but generally declined over time. The potent prime vaccination limited the detection of the boosting effect, and therefore, the effect of anti-vector immunity was not fully elucidated. These data show that PARVAX can be effectively re-administered and induce a novel antigenic response.

Introduction: Monitoring, Evaluation and Learning (MEL) is an integral part of research, programme and policy development and implementation. However, MEL methods used to monitor and evaluate interdisciplinary research projects are often informal and under-reported. This article describes the MEL protocol of the UKRI GCRF Action Against Stunting Hub (AASH)., Methods and Analysis: The AASH conducts interdisciplinary research into childhood stunting in India, Indonesia and Senegal across 23 distinct work packages. Project-specific MEL framework and methods will be implemented. A logframe will be developed to monitor and evaluate the research activities across the field sites including the number of participants recruited, questionnaires, measurements and procedures completed. MEL dashboards using Tableau and Glasscubes will be used to track and report progress, milestones and outcomes of the project. Dashboard outputs will be reported as numbers and percentages, with additional graphs/charts for easy visualisation. A 'learning' framework will be developed to outline appropriate pipelines for the dissemination of the research findings. This includes a theory of change explicating the overarching ambitions of the project in influencing policy, practice and research, and strategic engagement of relevant stakeholders to evaluate knowledge, attitudes and best practices for impactful engagement and dissemination of the research findings., Ethics and Dissemination: Ethical approval was granted by the Ethics Committee of the London School of Hygiene & Tropical Medicine (17915/RR/17513); National Institute of Nutrition (ICMR)-Ministry of Health and Family Welfare, Government of India (CR/04/I/2021); Health Research Ethics Committee, University of Indonesia and Cipto Mangunkusumo Hospital (KET-887/UN2.F1/ETIK/PPM.00.02/2019); and the National Ethics Committee for Health Research (CNERS), Senegal (Protocole SEN19/78). Findings from this work will be published in peer-reviewed journals, presented in conferences and disseminated to policy makers and research communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: One out of ten deaths of children under five are attributable to indoor air pollution. And Acute Respiratory Illness (ARI) is among the direct causes., Objective: This study showed the possibilities of characterizing indoor air pollution in West African Economic and Monetary Union (WAEMU) area and it also made it possible to estimate its impact on the occurrence of ARI in children under five., Methods: It has been a secondary analysis based on Demographic and Health Surveys (DHSs) from WAEMU countries' data.. "Household level of air pollution" is the created composite variable, from questions on the degradation factors of indoor air quality (domestic combustion processes) which served to characterize indoor air pollution and to measure its impact by a logistic regression., Results: Burkina Faso stands out with a greater number of households with a high level of pollution (63.7%) followed by Benin (43.7%) then Togo (43.0%). The main exposure factor "Household level of air pollution" was associated with ARI symptoms (Togo: prevalence = 51.3%; chi-squared test's p-value < 0.001). Exposure to high level of pollution constitutes a risk (AOR [95 CI]), even though it is not significant ( Ivory Coast: 1.29 [0.72-2.30], Senegal: 1.39 [0.94-2.05] and Togo: 1.15 [0.67-1.95]) and this could be explained by the high infectious etiology of the ARI., (© 2022. The Author(s).)

Marine pollution in West Africa is major threat particularly around coastal megacities. We assess the chemical and ecotoxicological quality of the marine sediments in various submerged sampling sites of Dakar. Analysis revealed that sediments were slightly basic in which fine and coarse sands predominated. High percentages of total organic carbon were found sometime above 6%. Higher levels of heavy metal were reported than in previous studies. Chromium and nickel were above the Probable Effect Concentration. Low trophic level appeared not affected by the overall toxicity, while medium trophic level was more affected. Indeed, the vast majority (91%) of sites studied revealed a net percentage of Magallana gigas embryolarval developmental abnormality over 20%. The assessment of the global toxicity of marine sediments from the Dakar sites Studied (n = 11) seemed, almost, as a whole, to be in a poor ecotoxicological state calling to take measures to improve the sanitary condition of this marine feature., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Gene therapy is emerging as a modality in 21st-century medicine. Adeno-associated viral (AAV) gene transfer is a leading technology to achieve efficient and durable expression of a therapeutic transgene. However, the structural complexity of the capsid has constrained efforts to engineer the particle toward improved clinical safety and efficacy. Here, we generate a curated library of barcoded AAVs with mutations across a variety of functionally relevant motifs. We then screen this library in vitro and in vivo in mice and nonhuman primates, enabling a broad, multiparametric assessment of every vector within the library. Among the results, we note a single residue that modulates liver transduction across all interrogated models while preserving transduction in heart and skeletal muscles. Moreover, we find that this mutation can be grafted into AAV9 and leads to profound liver detargeting while retaining muscle transduction-a finding potentially relevant to preventing hepatoxicities seen in clinical studies., Competing Interests: Declaration of interests L.H.V. holds equity in Affinia Therapeutics, Akouos, and ciendias bio. He serves on the Board of Directors of Affinia Therapeutics, Addgene, ciendias bio, and Odylia. L.H.V. is an employee of ciendias bio. L.H.V. and E.Z. are inventors of AncAAV technology licensed to Affinia, Akouos, and/or other biopharmaceutical companies from which they may receive royalties. L.H.V. is compensated for his scientific advisory position with Affinia and Akouos. L.H.V. is a SAB member to Akouos, consultant to Affinia and Novartis, and receives research support from Novartis. L.H.V.’s interests were reviewed and are managed by Mass Eye and Ear and Mass General Brigham in accordance with their conflict-of-interest policies. L.H.V., E.Z., C.U., P.F.S., C.T., and H.T.T. are inventors on patent applications relating to AAVSeq, CombiAAV, or the liver toggle technology contained in this publication. A.J.W. and L.H.V. are inventors on patents related to use of AAVs for therapeutic gene delivery in the muscle and other tissues., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Diarrheal diseases are the second leading cause of child mortality worldwide, occurring in about one in every nine child deaths, and were associated with water, sanitation, and hygiene (WASH) access. In this study, we provided an overview of WASH indicators' evolution from 2000 to 2017 and their impact on the occurrence of diarrhea in children under 5 years old in Senegal. It was a retrospective cross-sectional study, in which we did a secondary analysis of data from the Joint Monitoring Program (JMP) for water supply and sanitation and from the Senegal Demographic and Health Survey 2018. Our results showed that access to safely managed services increased by 18.1 and 19.1%, respectively, for water and sanitation. The prevalence of diarrhea estimated at 18.16% was associated with straining water through a cloth (adjusted odds ratio (AOR) [95% confidence interval (CI)]: 1.21 [1.00-1.45]) and getting water supplies from a source not located in a dwelling (AOR [95% CI]: 1.59 [1.21-2.09]). The prevalence of diarrhea among children under 5 years old was still relatively high in Senegal and was significantly associated with a lack of WASH access. Although the latter continues to increase, additional efforts to make water safer to drink will significantly reduce the occurrence of diarrheal diseases among children under 5 years old in Senegal.

The COVID-19 pandemic continues to have devastating consequences on health and economy, even after the approval of safe and effective vaccines. Waning immunity, the emergence of variants of concern, breakthrough infections, and lack of global vaccine access and acceptance perpetuate the epidemic. Here, we demonstrate that a single injection of an adenoassociated virus (AAV)-based COVID-19 vaccine elicits at least 17-month-long neutralizing antibody responses in non-human primates at levels that were previously shown to protect from viral challenge. To improve the scalability of this durable vaccine candidate, we further optimized the vector design for greater potency at a reduced dose in mice and non-human primates. Finally, we show that the platform can be rapidly adapted to other variants of concern to robustly maintain immunogenicity and protect from challenge. In summary, we demonstrate this class of AAV can provide durable immunogenicity, provide protection at dose that is low and scalable, and be adapted readily to novel emerging vaccine antigens thus may provide a potent tool in the ongoing fight against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)., Competing Interests: Declaration of interests J.M.W. is a paid advisor to and holds equity in Scout Bio and Passage Bio; he holds equity in Surmount Bio; he also has sponsored research agreements with Amicus Therapeutics, Biogen, Elaaj Bio, Janssen, Moderna, Passage Bio, Regeneron, Scout Bio, Surmount Bio, and Ultragenyx, which are licensees of Penn technology. L.H.V. and J.M.W. are inventors on patents that have been licensed to various biopharmaceutical companies and for which they may receive payments. L.H.V. is a paid advisor to Novartis, Akouos, and Affinia Therapeutics and serves on the Board of Directors of Affinia, Addgene, and Odylia Therapeutics. L.H.V. holds equity in Akouos and Affinia and receives sponsored research funding from Albamunity, to which he is an unpaid consultant. L.H.V. is co-founder and an employee of Ciendias Bio, a biotechnology company that pursues the development of AAV-based vaccines. L.H.V. further is a listed inventor on various gene transfer technologies, including some relevant to AAVCOVID. L.H.V. is a scientific advisory board member to Akouos, and board member of Affinia Therapeutics, companies of which he is a co-founder. U.B., N.Z. and L.H.V. are listed inventors on several patent applications on the described technologies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The SARS-CoV-2 pandemic has had a disastrous impact on global health. Although some vaccine candidates have been effective in combating SARS-CoV-2, logistical, economical, and sociological aspects still limit vaccine access globally. Recently, we reported on two room-temperature stable AAV-based COVID-19 vaccines that induced potent and protective immunogenicity following a single injection in murine and primate models. Obesity and old age are associated with increased mortality in COVID-19, as well as reduced immunogenicity and efficacy of vaccines. Here, we investigated the effectiveness of the AAVCOVID vaccine candidates in murine models of obesity and aging. Results demonstrate that obesity did not significantly alter the immunogenicity of either vaccine candidate. In aged mice, vaccine immunogenicity was impaired. These results suggest that AAV-based vaccines may have limitations in older populations and may be equally applicable in obese and non-obese populations.

The SARS-CoV-2 pandemic has affected more than 185 million people worldwide resulting in over 4 million deaths. To contain the pandemic, there is a continued need for safe vaccines that provide durable protection at low and scalable doses and can be deployed easily. Here, AAVCOVID-1, an adeno-associated viral (AAV), spike-gene-based vaccine candidate demonstrates potent immunogenicity in mouse and non-human primates following a single injection and confers complete protection from SARS-CoV-2 challenge in macaques. Peak neutralizing antibody titers are sustained at 1 year and complemented by functional memory T cell responses. The AAVCOVID vector has no relevant pre-existing immunity in humans and does not elicit cross-reactivity to common AAVs used in gene therapy. Vector genome persistence and expression wanes following injection. The single low-dose requirement, high-yield manufacturability, and 1-month stability for storage at room temperature may make this technology well suited to support effective immunization campaigns for emerging pathogens on a global scale., Competing Interests: Declaration of interests J.M.W. is a paid advisor to and holds equity in Scout Bio and Passage Bio; he holds equity in Surmount Bio; he also has sponsored research agreements with Amicus Therapeutics, Biogen, Elaaj Bio, Janssen, Moderna, Passage Bio, Regeneron, Scout Bio, Surmount Bio, and Ultragenyx, which are licensees of Penn technology. J.M.W. had a sponsored research agreement with Albamunity that funded this work. He also has a sponsored research agreement with G2 Bio. L.H.V. and J.M.W. are inventors on patents that have been licensed to various biopharmaceutical companies and for which they may receive payments including vector and vaccine technologies herein described. L.H.V., W.D., U.B., N.Z. are named inventors on two patent applications relevant to AAVCOVID. W.Q., E.H., S.Y., and R.H. are employees of Novartis. M.W.F. is a paid consultant to 5AM Ventures and to Mitobridge/Astellas. L.H.V. is a paid advisor to Novartis, Akouos, and Affinia Therapeutics and serves on the Board of Directors of Affinia, Addgene, and Odylia Therapeutics. L.H.V. holds equity in Akouos and Affinia and receives sponsored research funding from Albamunity Inc. to which he is an unpaid consultant. M.R.B. receives consulting fees from Interius Biotherapeutics. R.C.L. is a subcontractor with the CDC Foundation and receives royalties from UpToDate., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The SARS-CoV-2 pandemic has affected more than 70 million people worldwide and resulted in over 1.5 million deaths. A broad deployment of effective immunization campaigns to achieve population immunity at global scale will depend on the biological and logistical attributes of the vaccine. Here, two adeno-associated viral (AAV)-based vaccine candidates demonstrate potent immunogenicity in mouse and nonhuman primates following a single injection. Peak neutralizing antibody titers remain sustained at 5 months and are complemented by functional memory T-cells responses. The AAVrh32.33 capsid of the AAVCOVID vaccine is an engineered AAV to which no relevant pre-existing immunity exists in humans. Moreover, the vaccine is stable at room temperature for at least one month and is produced at high yields using established commercial manufacturing processes in the gene therapy industry. Thus, this methodology holds as a very promising single dose, thermostable vaccine platform well-suited to address emerging pathogens on a global scale.

Concentrations of 11 elements (As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se,V and Zn) were quantified in liver and muscle from two commercially important fish species from the Senegalese coast. The fish, a small pelagic species (the round sardinella) and a benthic species (the Senegalese sole) were collected from five sites during the dry and wet seasons in 2013. For both species, elements were more concentrated in liver than in muscle. There was no clear seasonal pattern in concentration of elements, however inter-site differences were observed. We found significant differences in element concentrations between the two studied species, likely associated with their behavior, feeding and habitat use. The concentrations of Cd, Fe, and Pb were significantly higher in sardinella whereas concentration of As, Cu, Cr, Mn and Se were highest in sole. The concentration of cadmium was particularly high in the liver of sardinella (from 0.9 to 56 mg kg(-1), with a mean ± sd of 17.2 ± 11.5 mg kg(-1)) and may be related to anthropogenic pressure such as the phosphate industry but also to the upwelling current which brings dissolved elements to the surface that are taken up by plankton. The results showed that concentrations of Cd and Pb were below the limit values established by the European Community and pose no threat to public health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The purpose of the study was to determine Pb and Cd concentrations in humans and to assess the effect of co-exposure to these metals on biomarkers of oxidative stress and nephrotoxicity. Blood and urine levels of Pb and Cd, oxidative stress and urinary renal biomarkers were measured in 77 subjects neighboring a discharge and 52 in the control site. Exposed subjects showed significantly higher levels of lead and cadmium in blood and urine than the controls. Excessive production of reactive oxygen species induced by these metals in exposed subjects conducted to a decrease in antioxidant defense system (GPx, Selenium, GSH) and an increase in lipid peroxidation (MDA). Moreover, changes in markers of nephrotoxicity (high urinary concentrations of total protein, RBP and CC16, as well as GSTα and LDH increased activities) suggested the occurrence of discrete and early signs of impaired renal function for the discharge neighboring population., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Trace metals have the potential to associate with sediments that have been recognised as significant source of contamination for the benthic environment. The current study aims assessing the trace metals contamination level in sediments from Dakar coast and Saint Louis estuary, and to examine their bioavailability to predict potential toxicity of sediments. Surface sediment samples were collected between June 2012 and January 2013 in three sampling periods from eight stations. Trace metals were analysed using inductively coupled plasma-optical emission spectrometer. Geoaccumulation indexes (Igeo) showed strong pollution by Cd, Cr, Cu and Pb confirmed by enrichment factor (EF) suggesting that these metals derived from anthropogenic sources. Toxicity indexes exceeded one in several sites suggesting the potential effects on sediment-dwelling organisms, which may constitute a risk to populations' health. However, seasonal variability of metal bioavailability was noted, revealing the best period to monitor metal contamination. From an ecotoxicological point of view, concentrations of Cd, Cr, Cu and Pb were above the effects range low threshold limit of the sediment quality guidelines for adverse biological effects. In addition, with Pb concentrations above the effect range medium values in some sites, biological effects may occur., (Copyright © 2014 Elsevier Ltd. All rights reserved.)