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1.
Security and Communication Networks ; 2023, 2023.
Article in English | Scopus | ID: covidwho-20243671

ABSTRACT

Electronic health records (EHRs) and medical data are classified as personal data in every privacy law, meaning that any related service that includes processing such data must come with full security, confidentiality, privacy, and accountability. Solutions for health data management, as in storing it, sharing and processing it, are emerging quickly and were significantly boosted by the COVID-19 pandemic that created a need to move things online. EHRs make a crucial part of digital identity data, and the same digital identity trends - as in self-sovereign identity powered by decentralized ledger technologies like blockchain, are being researched or implemented in contexts managing digital interactions between health facilities, patients, and health professionals. In this paper, we propose a blockchain-based solution enabling secure exchange of EHRs between different parties powered by a self-sovereign identity (SSI) wallet and decentralized identifiers. We also make use of a consortium IPFS network for off-chain storage and attribute-based encryption (ABE) to ensure data confidentiality and integrity. Through our solution, we grant users full control over their medical data and enable them to securely share it in total confidentiality over secure communication channels between user wallets using encryption. We also use DIDs for better user privacy and limit any possible correlations or identification by using pairwise DIDs. Overall, combining this set of technologies guarantees secure exchange of EHRs, secure storage, and management along with by-design features inherited from the technological stack. © 2023 Marie Tcholakian et al.

2.
Revue d'Epidemiologie et de Sante Publique ; Conference: Congres national Emois 2023. Nancy France. 71(Supplement 1) (no pagination), 2023.
Article in French | EMBASE | ID: covidwho-2302186

ABSTRACT

Introduction: La mortalite des residents d'Ehpad (Etablissement pour personnes agees dependantes) a augmente de 43 % pendant la premiere vague de COVID-19. Nous avons estime l'heterogeneite inter-Ehpad de la mortalite et identifie les facteurs de risque de deces durant cette periode, comparativement a 2019. Methodes: Dans deux cohortes de residents d'Ehpad geres par le regime general en France metropolitaine (donnees de RESIDESMS du 01/03/2020 au 31/05/2020 et du 01/03/2019 au 31/05/2019), l'heterogeneite inter-Ehpad de la mortalite etait mesuree dans une regression logistique mixte par le coefficient de correlation intraclasse (CCI). Les facteurs etudies comprenaient les caracteristiques des residents, notamment les pathologies reperees par la Cartographie des pathologies du Systeme national des donnees de sante (SNDS), et celles liees a l'Ehpad, notamment le departement et le statut public/prive. Le CCI a egalement ete estime separement dans les Ehpad avec aucun ou au moins un deces avec mention de COVID-19. Resultats: Parmi 385 300 residents (5339 Ehpad) inclus en 2020 (age median: 89 ans, 25 % d'hommes), 9,1 % sont decedes, contre 6,7 % des 379 926 residents (5270 Ehpad) en 2019. Dans le modele vide, le CCI etait de 9,3 % en 2020 et de 1,5 % en 2019. Seul le departement expliquait partiellement l'heterogeneite observee en 2020 (CCI: 6,5 % apres ajustement). Les associations etaient plus fortes en 2020 qu'en 2019 pour le sexe masculin et le diabete et plus faibles pour les cardiopathies, les maladies respiratoires chroniques et la residence <6 mois. Dans les Ehpad avec au moins 1 deces avec mention de COVID-19, la mortalite etait plus elevee en 2020 (15,1 %) qu'en 2019 (6,3 %) et plus heterogene (CCI: 8,0 %) que dans les autres (mortalite: 6,7 % les deux annees;CCI: 1,1 %). Discussion/Conclusion: Nous avons observe une heterogeneite inter-Ehpad de la mortalite lors de la premiere vague en 2020 qui n'existait pas en 2019, non expliquee par les caracteristiques des Ehpad, excepte le departement. Ce resultat renvoie a la geographie de la diffusion du SARS-CoV-2. L'heterogeneite inter-Ehpad semblait peu concerner les Ehpad non atteintes par la pandemie. Mots-cles: Personnes agees;Mortalite;COVID-19;Ehpad Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets.Copyright © 2023

3.
Revue d'epidemiologie et de sante publique ; 71(1):101504-101504, 2023.
Article in French | EuropePMC | ID: covidwho-2277363

ABSTRACT

Introduction La mortalité des résidents d'Ehpad (Etablissement pour personnes âgées dépendantes) a augmenté de 43 % pendant la première vague de COVID-19. Nous avons estimé l'hétérogénéité inter-Ehpad de la mortalité et identifié les facteurs de risque de décès durant cette période, comparativement à 2019. Méthodes Dans deux cohortes de résidents d'Ehpad gérés par le régime général en France métropolitaine (données de RESIDESMS du 01/03/2020 au 31/05/2020 et du 01/03/2019 au 31/05/2019), l'hétérogénéité inter-Ehpad de la mortalité était mesurée dans une régression logistique mixte par le coefficient de corrélation intraclasse (CCI). Les facteurs étudiés comprenaient les caractéristiques des résidents, notamment les pathologies repérées par la Cartographie des pathologies du Système national des données de santé (SNDS), et celles liées à l'Ehpad, notamment le département et le statut public/privé. Le CCI a également été estimé séparément dans les Ehpad avec aucun ou au moins un décès avec mention de COVID-19. Résultats Parmi 385 300 résidents (5339 Ehpad) inclus en 2020 (âge médian: 89 ans, 25 % d'hommes), 9,1 % sont décédés, contre 6,7 % des 379 926 résidents (5270 Ehpad) en 2019. Dans le modèle vide, le CCI était de 9,3 % en 2020 et de 1,5 % en 2019. Seul le département expliquait partiellement l'hétérogénéité observée en 2020 (CCI: 6,5 % après ajustement). Les associations étaient plus fortes en 2020 qu'en 2019 pour le sexe masculin et le diabète et plus faibles pour les cardiopathies, les maladies respiratoires chroniques et la résidence <6 mois. Dans les Ehpad avec au moins 1 décès avec mention de COVID-19, la mortalité était plus élevée en 2020 (15,1 %) qu'en 2019 (6,3 %) et plus hétérogène (CCI: 8,0 %) que dans les autres (mortalité: 6,7 % les deux années;CCI: 1,1 %). Discussion/Conclusion Nous avons observé une hétérogénéité inter-Ehpad de la mortalité lors de la première vague en 2020 qui n'existait pas en 2019, non expliquée par les caractéristiques des Ehpad, excepté le département. Ce résultat renvoie à la géographie de la diffusion du SARS-CoV-2. L'hétérogénéité inter-Ehpad semblait peu concerner les Ehpad non atteintes par la pandémie. Mots-clés Personnes âgées ;Mortalité ;COVID-19 ;Ehpad Déclaration de liens d'intérêts Les auteurs déclarent ne pas avoir de liens d'intérêts.

4.
Annales Francaises de Medecine d'Urgence ; 10(4-5):218-223, 2020.
Article in French | ProQuest Central | ID: covidwho-2252004

ABSTRACT

La crise sanitaire Covid-19 a obligé les Samu–Smur à adapter leurs organisations au jour le jour. La régulation a dû trouver des réponses spécifiques aux types d'appels, au plan quantitatif et qualitatif. En lien avec la médecine générale et les recommandations ministérielles, le Samu devait être le garant d'une juste orientation des patients vers les services hospitaliers. Le Samu 94 et la faculté de santé de Créteil ont créé une cellule dédiée aux établissements d'hébergement des personnes âgées dépendantes, accessible via une ligne spécialisée du Samu–centre 15, offrant 24 heures/24 l'accès à des compétences gériatriques et conseils divers, véritable lien ville–hôpital. Le retour d'expérience montre que cette cellule est une des facettes, dans le domaine de la gériatrie, de ce qu'est le concept de service d'accès aux soins (SAS) et qu'il ne faut pas attendre un rebond de crise pour en consolider les fondements.Alternate : The COVID-19 health crisis forced the French emergency call centers (SAMU), and related prehospital medical mobile teams, to quickly adapt and reorganize on a daily basis. Call centers had to come up with specific responses to all types of calls, as well as to manage quantitative increases in call intakes, and to maintain high qualitative standards. In collaboration with general practices, and aligned on ministerial recommendations, the SAMU was to be the gatekeeper of the surge in referrals of elderly patients to in-hospital emergency departments. SAMU 94 and the health faculty of the University of Créteil, France, jointly set up an online unit dedicated to nursing homes, accessible via a specific SAMU telephone line. It offered 24/7 access to geriatric expertise and advice, and aimed to strengthen the chain of care between general practices and hospitals. Feedback shows that this geriatric unit is one of the facets of the healthcare access system that the innovative French SAS relies on, and that we should not wait for a second-wave crisis to consolidate its foundations.

5.
Ieee Access ; 10:106400-106414, 2022.
Article in English | Web of Science | ID: covidwho-2083046

ABSTRACT

This paper introduces SPOT, a Secure and Privacy-preserving prOximity based protocol for e-healthcare systems. It relies on a distributed proxy-based approach to preserve users' privacy and a semi-trusted computing server to ensure data consistency and integrity. The proposed protocol ensures a balance between security, privacy and scalability. As far as we know, in terms of security, SPOT is the first one to prevent malicious users from colluding and generating false positives. In terms of privacy, SPOT supports both anonymity of users being in proximity of infected people and unlinkability of contact information issued by the same user. A concrete construction based on structure-preserving signatures and NIWI proofs is proposed and a detailed security and privacy analysis proves that SPOT is secure under standard assumptions. In terms of scalability, SPOT's procedures and algorithms are implemented to show its efficiency and practical usability with acceptable computation and communication overhead.

6.
Neurol Res Pract ; 4(1): 44, 2022 Sep 22.
Article in English | MEDLINE | ID: covidwho-2039136

ABSTRACT

BACKGROUND: To mitigate the potential consequences of the coronavirus disease 2019 (COVID-19) pandemic on public life, the German Federal Government and Ministry of Health enacted a strict lockdown protocol on March 16, 2020. This study aimed to evaluate the impact of the COVID-19 pandemic on physical and mental health status and the supply of medical care and medications for people with epilepsy (PWE) in Germany. METHODS: The Epi2020 study was a large, multicenter study focused on different healthcare aspects of adults with epilepsy. In addition to clinical and demographic characteristics, patients were asked to answer a questionnaire on the impact of the first wave of the COVID-19 pandemic between March and May 2020. Furthermore, the population-based number of epilepsy-related admissions in Hessen was evaluated for the January-June periods of 2017-2020 to detect pandemic-related changes. RESULTS: During the first wave of the pandemic, 41.6% of PWE reported a negative impact on their mental health, while only a minority reported worsening of their seizure situation. Mental and physical health were significantly more negatively affected in women than men with epilepsy and in PWE without regular employment. Moreover, difficulties in ensuring the supply of sanitary products (25.8%) and antiseizure medications (ASMs; 19.9%) affected PWE during the first lockdown; no significant difference regarding these impacts between men and women or between people with and without employment was observed. The number of epilepsy-related admissions decreased significantly during the first wave. CONCLUSIONS: This analysis provides an overview of the general and medical care of epilepsy patients during the COVID-19 pandemic. PWE in our cohort frequently reported psychosocial distress during the first wave of the pandemic, with significant adverse effects on mental and physical health. Women and people without permanent jobs especially reported distress due to the pandemic. The COVID-19 pandemic has added to the mental health burden and barriers to accessing medication and medical services, as self-reported by patients and verified in population-based data on hospital admissions. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS00022024. Registered October 2, 2020, http://www.drks.de/DRKS00022024.

7.
Médecine et Maladies Infectieuses Formation ; 1(2, Supplement):S58, 2022.
Article in English | ScienceDirect | ID: covidwho-1867537

ABSTRACT

Introduction De nombreux patients sont encore insuffisamment vaccinés pour la COVID-19 que ce soit pour la primovaccination et ou le rappel. Les raisons de cette non-vaccination sont nombreuses mais, outre le refus de patients par conviction, un certain nombre de patients isolés (personne âgée, barrière de langue, méconnaissance de schéma vaccinal spécifique…) n'ont pu accéder à cette vaccination en ville. L'hospitalisation est une porte d'entrée pour l'identification de ces patients et une proposition vaccinale. Nous avons implémenté une organisation hospitalière pérenne à partir de juin 2021 afin de proposer une possibilité de vaccination aux médecins hospitaliers qui souhaitaient proposer cette vaccination à leurs patients. Cette étude vise à évaluer l'efficacité de cette organisation de mai à décembre 2021. Matériels et méthodes Pour les patients éligibles et volontaires, les médecins commandaient une dose le vaccin BNT162b2 (Comirnaty® ; BioNTech Pfizer)à la pharmacie hospitalière (PUI). Après validation pharmaceutique, la préparation de la dose était programmée par la PUI. Les doses étaient administrées par les infirmières en services de soins. La vaccination était renseignée par le pharmacien via le téléservice "Vaccin Covid". Tous les patients vaccinés ont été inclus. Pour évaluer la population éligible à cette vaccination nous avons comptabilisé tous les patients hospitalisés pendant la même période en excluant les patients hospitalisés en unité COVID, pédiatrie, Soins Continus et réanimation, pour moins de 24h (patients non éligibles), ou en chirurgie (organisation vaccinale non implémentée) Résultats Entre mai et décembre 2021, 352 doses de vaccins COVID-19 ont été délivrées. Le délai médian de mise à disposition du vaccin était de 1 jour après commande. Le nombre mensuel de doses délivrées variait entre 29 et 60. Parmi ces 352 doses, on comptabilisait 203 premières doses (58 %), 149 doses de rappel (42 %) (2ème ou 3ème dose). 245 (70 %) doses ont été administrées à des patients âgés de plus de 65 ans. Ces 352 doses ont été administrées à 187 patients hospitalisés et 65 patients issus de cohorte de patients chroniques notamment hémodialysés ou présentant une hémopathie, dont 55 ont reçu leur schéma vaccinal complet au sein de notre établissement. Nous avons rapporté la proportion de patients vaccinés hospitalisés au sein de la population totale hospitalisée potentiellement éligible pendant la période d'étude. 4791patients ont été hospitalisés dans une unité ou la vaccination était réalisable, 3,9 % des patients hospitalisés ont donc bénéficié d'une dose de vaccin BNT162b2, avec une proportion bien plus élevée de patients réellement éligibles c-à-d n'ayant in fine pas un schéma vaccinal complet. Conclusion Ces résultats montrent la faisabilité et l'intérêt de la vaccination COVID-19 au sein des hôpitaux pour les patients hospitalisés fragiles. Cette vaccination de patients hospitalisés permet d'améliorer la couverture vaccinale des patients les plus fragiles et de diminuer la proportion de patients insuffisamment vaccinés en milieu hospitalier. La constitution de CHV peut être un outil important d'amélioration de la couverture vaccinale des populations les plus à risque à risque pour la COVID et probablement d'autres pathologies Aucun lien d'intérêt

8.
Vaccine ; 40(21): 2960-2969, 2022 05 09.
Article in English | MEDLINE | ID: covidwho-1773836

ABSTRACT

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of T cells and antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibody Formation , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Macaca mulatta , Mice , Mice, Inbred BALB C , SARS-CoV-2 , Vaccination
9.
Journal of Public Health and Epidemiology ; 13(4):262-271, 2021.
Article in English | GIM | ID: covidwho-1726669

ABSTRACT

The epidemiological, clinical and therapeutic outcomes of COVID-19 vary across countries from March 16th to July 30, 2020, 1805 cases were registered in Benin, and among these cases, about 36 deaths occurred. The aim of this work was to study the epidemiological and clinical features associated with the survival of people with COVID-19 in the Department of Littoral in Republic of Benin, from March to July 2020. This was an analytical cross-sectional study that involved 920 cases of COVID-19. The Kaplan Meier method was used to estimate the survival probability and the cumulative death risk in COVID-19 cases. The Cox model was able to identify associated factors with death caused by COVID- 19. The median age was 37 (Q1=28;Q3=48) years ranging from 3 to 84;the sex ratio was 0.85 in women's favor. Most of affected people had a university level of educational attainment (64.02%). The survival probability of patients was 99% 95%CI: [98.4-99.5] at seven days, and 97.7% 95%CI: [96.4-98.5] at 17 days and more. Age (RRadjusted;95%CI: 6.29;[1.04-37.79]), educational attainment (RRadjusted;95%CI: 0.11;[0.01-0.95]), place of treatment (RRadjusted;95%CI: 18.70;[1.27-274.46]) and treatment received (RRadjusted;95%CI: 238.46;[19.18-2963.77]) were significantly associated with treatment outcome. In conclusion, in the early stage of COVID-19 outreach in the Department of Littoral of Benin, a high level of education showed to be a protective factor against poor outcome of the treatment. Health education and promotion of school attendance remained key strategies to prevent disease in Benin.

10.
Int J Environ Res Public Health ; 19(3)2022 02 02.
Article in English | MEDLINE | ID: covidwho-1667170

ABSTRACT

During COVID-19 pandemic peaks, healthcare professionals are a frontline workforce that deals with death on an almost daily basis and experiences a marked increase in workload. Returning home is also associated with fear of contaminating or be contaminated. An obvious consequence is stress accumulation and associated risks, especially in caregivers in mobility and possibly in human resource teams managing mobility. Here, during the second pandemic peak, we designed a 15-min testing procedure at the workplace, combining HADS and Brief COPE questionnaires with heart rate variability (HRV) recordings to evaluate psychophysiological status in four groups: caregivers in mobility (MOB); human resources teams managing mobility (ADM); caregivers without mobility (N-MOB); and university researchers teaching online (RES). Anxiety, depression, coping strategies, vagally-mediated heart rate regulation, and nonlinear dynamics (entropy) in cardiac autonomic control were quantified. Anxiety reached remarkably high levels in both MOB and ADM, which was reflected in vagal and nonlinear HRV markers. ADM maintained a better problem-solving capacity. MOB and N-MOB exhibited degraded problem-solving capacity. Multivariate approaches show how combining psychological and physiological markers helps draw highly group-specific psychophysiological profiles. Entropy in HRV and problem-solving capacity were highly relevant for that. Combining HADS and Brief COPE questionnaires with HRV testing at the workplace may provide highly relevant cues to manage mobility during crises as well as prevent health risks, absenteeism, and more generally malfunction incidents at hospitals.


Subject(s)
COVID-19 , Caregivers , Heart Rate , Humans , Pandemics , SARS-CoV-2 , Workforce , Workplace
11.
Cell Rep ; 38(5): 110318, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1654152

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines may target epitopes that reduce durability or increase the potential for escape from vaccine-induced immunity. Using synthetic vaccinology, we have developed rationally immune-focused SARS-CoV-2 Spike-based vaccines. Glycans can be employed to alter antibody responses to infection and vaccines. Utilizing computational modeling and in vitro screening, we have incorporated glycans into the receptor-binding domain (RBD) and assessed antigenic profiles. We demonstrate that glycan-coated RBD immunogens elicit stronger neutralizing antibodies and have engineered seven multivalent configurations. Advanced DNA delivery of engineered nanoparticle vaccines rapidly elicits potent neutralizing antibodies in guinea pigs, hamsters, and multiple mouse models, including human ACE2 and human antibody repertoire transgenics. RBD nanoparticles induce high levels of cross-neutralizing antibodies against variants of concern with durable titers beyond 6 months. Single, low-dose immunization protects against a lethal SARS-CoV-2 challenge. Single-dose coronavirus vaccines via DNA-launched nanoparticles provide a platform for rapid clinical translation of potent and durable coronavirus vaccines.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Nanoparticles/administration & dosage , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/immunology , Binding Sites , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/genetics , Cricetinae , Epitopes , Guinea Pigs , Immunogenicity, Vaccine , Mice , Nanoparticles/chemistry , Nucleic Acid-Based Vaccines/administration & dosage , Nucleic Acid-Based Vaccines/chemistry , Nucleic Acid-Based Vaccines/genetics , Nucleic Acid-Based Vaccines/immunology , Polysaccharides/chemistry , Polysaccharides/genetics , Polysaccharides/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccine Potency
12.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.10.27.466163

ABSTRACT

The enhanced transmissibility and immune evasion associated with emerging SARS-CoV-2 variants demands the development of next-generation vaccines capable of inducing superior protection amid a shifting pandemic landscape. Since a portion of the global population harbors some level of immunity from vaccines based on the original Wuhan-Hu-1 SARS-CoV-2 sequence or natural infection, an important question going forward is whether this immunity can be boosted by next-generation vaccines that target emerging variants while simultaneously maintaining long-term protection against existing strains. Here, we evaluated the immunogenicity of INO-4800, our synthetic DNA vaccine candidate for COVID-19 currently in clinical evaluation, and INO-4802, a next-generation DNA vaccine designed to broadly target emerging SARS-CoV-2 variants, as booster vaccines in nonhuman primates. Rhesus macaques primed over one year prior with the first-generation INO-4800 vaccine were boosted with either INO-4800 or INO-4802 in homologous or heterologous prime-boost regimens. Both boosting schedules led to an expansion of antibody responses which were characterized by improved neutralizing and ACE2 blocking activity across wild-type SARS-CoV-2 as well as multiple variants of concern. These data illustrate the durability of immunity following vaccination with INO-4800 and additionally support the use of either INO-4800 or INO-4802 in prime-boost regimens.


Subject(s)
COVID-19
13.
NPJ Vaccines ; 6(1): 121, 2021 Oct 14.
Article in English | MEDLINE | ID: covidwho-1469970

ABSTRACT

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine-induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFNγ T cell responses were fully maintained against all variants tested.

14.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.10.06.21264584

ABSTRACT

Background: Additional SARS-CoV-2 vaccines that are safe and effective as both primary series and booster remain urgently needed to combat the COVID-19 pandemic. Here we describe the safety and durability of the immune response from two doses of a DNA vaccine (INO-4800) targeting the full-length Spike antigen and a subsequent homologous booster dose. Methods: INO-4800 was evaluated in 120 healthy participants across three dose groups (0.5 mg, 1.0 mg and 2.0 mg), each stratified by age. INO-4800 was injected intradermally followed by electroporation at 0 and 4 weeks followed by an optional booster dose 6-10.5 months following the second dose. Results: INO-4800 was well-tolerated, with no treatment-related serious adverse events reported. Most adverse events were mild in severity and did not increase in frequency with age and subsequent dosing. A durable antibody response was observed 6 months following the second dose; a homologous booster dose significantly increased immune responses. Cytokine producing T cells and activated CD8+T cells with lytic potential were detected in the 2.0 mg dose group. Conclusion: INO-4800 was well-tolerated as a 2-dose series and as a homologous booster dose in all adults, including the elderly. These results support further development of INO-4800 as a primary series and as a booster. Keywords: SARS-CoV-2; Clinical trial; DNA Vaccine; COVID-19; Immunogenicity; Booster


Subject(s)
COVID-19
15.
Cell Rep Med ; 2(10): 100420, 2021 10 19.
Article in English | MEDLINE | ID: covidwho-1450242

ABSTRACT

Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health and social and economic infrastructures. Here, we assess the immunogenicity and anamnestic protective efficacy in rhesus macaques of an intradermal (i.d.)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800, currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and induced spike antigen and RBD binding antibodies with ADCP and ADCD activity. Sera from the animals neutralized both the D614 and G614 SARS-CoV-2 pseudotype viruses. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T cell and neutralizing antibody responses. These responses were associated with lower viral loads in the lung. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system, which are likely important for providing durable protection against COVID-19 disease.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Lung/virology , T-Lymphocytes/immunology , Animals , Antibodies, Neutralizing/blood , COVID-19 Vaccines/therapeutic use , Female , Injections, Intradermal , Macaca mulatta , Male , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/therapeutic use , Viral Load
16.
Vaccine ; 39(34): 4885-4894, 2021 08 09.
Article in English | MEDLINE | ID: covidwho-1284599

ABSTRACT

Safe and effective vaccines will provide essential medical countermeasures to tackle the COVID-19 pandemic. Here, we assessed the safety, immunogenicity and efficacy of the intradermal delivery of INO-4800, a synthetic DNA vaccine candidate encoding the SARS-CoV-2 spike protein in the rhesus macaque model. Single and 2 dose vaccination regimens were evaluated. Vaccination induced both binding and neutralizing antibodies, along with IFN-γ-producing T cells against SARS-CoV-2. Upon administration of a high viral dose (5 × 106 pfu) via the intranasal and intratracheal routes we observed significantly reduced virus load in the lung and throat, in the vaccinated animals compared to controls. 2 doses of INO-4800 was associated with more robust vaccine-induced immune responses and improved viral protection. Importantly, histopathological examination of lung tissue provided no indication of vaccine-enhanced disease following SARS-CoV-2 challenge in INO-4800 immunized animals. This vaccine candidate is currently under clinical evaluation as a 2 dose regimen.


Subject(s)
COVID-19 , Vaccines, DNA , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , Humans , Macaca mulatta , Pandemics , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
17.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.05.11.443592

ABSTRACT

First generation COVID-19 vaccines matched to the original Wuhan-Hu-1 (WT) strain are showing reduced efficacy against emerging SARS-CoV-2 variants of concern (VOC). In response, next generation vaccines either matched to a single variant or designed to provide broader coverage across the VOC group are being developed. The latter pan-SARS-CoV-2 approach may offer substantial advantages in terms of cross-strain protection, immune coverage, reduced susceptibility to escape mutants, and non-restricted geographical use. Here we have employed our SynCon(R) design technology to construct a DNA vaccine expressing a pan-Spike immunogen (INO-4802) to induce broad immunity across SARS-CoV-2 variants. Compared to WT and VOC-matched vaccines which showed limited cross-neutralizing activity, INO-4802 induced potent neutralizing antibodies and T cell responses against WT as well as B.1.1.7, P.1, and B.1.351 VOCs in a murine model. In addition, a hamster vaccination model showed enhanced humoral responses against VOCs in a heterologous pWT prime/INO-4802 boost setting. These results demonstrate the potential of the pan-SARS-CoV-2 vaccine, INO-4802 to induce cross-reactive immune responses against emerging VOCs as either a standalone vaccine, or as a potential boost for individuals previously immunized with WT-matched vaccines.


Subject(s)
COVID-19
18.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.05.07.21256652

ABSTRACT

Background: Vaccines against SARS-CoV-2 are still urgently needed as only 5% of the global population has been vaccinated. Here we report the safety and immunogenicity of a DNA vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2 when given to adults at high-risk of exposure. Methods: INO-4800 was evaluated in 401 participants randomized at a 3:3:1:1 ratio to receive either INO-4800 (1 mg or 2 mg dose) or placebo (1 or 2 injections) intradermally followed by electroporation (EP) using CELLECTRA 2000 at Days 0 and 28. ClinicalTrials.gov Identifier: NCT04642638 Findings: The majority of adverse events (AEs) were of Grade 1 and 2 in severity and did not appear to increase in frequency with the second dose. The number of participants experiencing each of the most common AEs did not differ appreciably between the two dosing groups. The geometric mean fold rise (GMFR) of binding and neutralizing antibody levels were statistically significantly greater in the 2.0 mg dose group versus the 1.0 mg dose group. The T cell immune responses measured by the ELISpot assay were also higher in the 2.0 mg dose group compared to the 1.0 mg dose group. Interpretation: INO-4800 at both the 1.0 mg and 2.0 mg doses when administered in a 2-dose regimen appeared to be safe and well-tolerated in all adult ages. However, the comparative immunogenicity analysis favored selection of INO-4800 2.0 mg dose for advancement into a Phase 3 efficacy evaluation. Funding: The Department of Defense, Joint Program Executive Office provided funding for the Phase 2 segment of the trial

19.
JCI Insight ; 6(10)2021 05 24.
Article in English | MEDLINE | ID: covidwho-1197299

ABSTRACT

Emerging coronaviruses from zoonotic reservoirs, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been associated with human-to-human transmission and significant morbidity and mortality. Here, we study both intradermal and intramuscular 2-dose delivery regimens of an advanced synthetic DNA vaccine candidate encoding a full-length MERS-CoV spike (S) protein, which induced potent binding and neutralizing antibodies as well as cellular immune responses in rhesus macaques. In a MERS-CoV challenge, all immunized rhesus macaques exhibited reduced clinical symptoms, lowered viral lung load, and decreased severity of pathological signs of disease compared with controls. Intradermal vaccination was dose sparing and more effective in this model at protecting animals from disease. The data support the further study of this vaccine for preventing MERS-CoV infection and transmission, including investigation of such vaccines and simplified delivery routes against emerging coronaviruses.


Subject(s)
Coronavirus Infections/veterinary , Macaca mulatta/immunology , Middle East Respiratory Syndrome Coronavirus/immunology , Vaccines, DNA/therapeutic use , Viral Vaccines/therapeutic use , Animals , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Injections, Intradermal , Middle East Respiratory Syndrome Coronavirus/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Vaccines, DNA/administration & dosage , Vaccines, DNA/genetics , Viral Vaccines/administration & dosage , Viral Vaccines/genetics
20.
biorxiv; 2021.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2021.04.14.439719

ABSTRACT

Global surveillance has identified emerging SARS-CoV-2 variants of concern (VOC) associated with broadened host specificity, pathogenicity, and immune evasion to vaccine induced immunity. Here we compared humoral and cellular responses against SARS-CoV-2 VOC in subjects immunized with the DNA vaccine, INO-4800. INO-4800 vaccination induced neutralizing antibodies against all variants tested, with reduced levels detected against B.1.351. IFN{gamma} T cell responses were fully maintained against all variants tested.

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