Resources, Production Scales and Time Required for Producing RNA Vaccines for the Global Pandemic Demand

Vaccines, Journal Year: 2020, Volume and Issue: 9(1), P. 3 - 3

Published: Dec. 23, 2020

To overcome pandemics, such as COVID-19, vaccines are urgently needed at very high volumes. Here we assess the techno-economic feasibility of producing RNA for demand associated with a global vaccination campaign. Production process performance is assessed three messenger (mRNA) and one self-amplifying (saRNA) vaccines, all currently under clinical development, well hypothetical next-generation saRNA vaccine. The impact key design operation uncertainties on production was assessed. vaccine drug substance (DS) rates, volumes costs mostly impacted by amount per dose to lesser extent scale titre in process. resources, speed required meet vary substantially function dose. For lower can be met using below 10 L bioreactor working volume. Consequently, these small-scale processes require low resources set up operate. DS faster than fill-to-finish into multidose vials; hence latter may constitute bottleneck.

Language: Английский

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A Brief Review on Dna Vaccines in the Era of COVID-19

Future Virology, Journal Year: 2021, Volume and Issue: 17(1), P. 49 - 66

Published: Nov. 26, 2021

This article provides a brief overview of DNA vaccines. First, the basic vaccine design strategies are described, then specific issues related to industrial production vaccines discussed, including and purification products such as plasmid DNA, minicircle minimalistic, immunologically defined gene expression (MIDGE) Doggybone™. The use adjuvants enhance immunogenicity is discussed. In addition, different delivery routes several physical chemical methods increase efficacy into cells explained. Recent preclinical clinical trials for COVID-19 summarized. Lastly, advantages obstacles

Language: Английский

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Peptides for Vaccine Development

ACS Applied Bio Materials, Journal Year: 2022, Volume and Issue: 5(3), P. 905 - 944

Published: Feb. 23, 2022

This review discusses peptide epitopes used as antigens in the development of vaccines clinical trials well future vaccine candidates. It covers peptides potential immunotherapies for infectious diseases including SARS-CoV-2, influenza, hepatitis B and C, HIV, malaria, others. In addition, cancer that target examples overexpressed proteins are summarized, human epidermal growth factor receptor 2 (HER-2), mucin 1 (MUC1), folate receptor, The uses to cancers caused by infective agents, example, cervical papilloma virus (HPV), also discussed. provides an overview model stimulate non-specific immune responses, self-adjuvanting peptides, influence other adjuvants on formulations. As highlighted this review, several advanced vaccines, there is great therapies due specificity response can be achieved using epitopes.

Language: Английский

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Sterilizing Immunity against SARS‐CoV‐2 Infection in Mice by a Single‐Shot and Lipid Amphiphile Imidazoquinoline TLR7/8 Agonist‐Adjuvanted Recombinant Spike Protein Vaccine**

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(17), P. 9467 - 9473

Published: Jan. 19, 2021

Abstract The search for vaccines that protect from severe morbidity and mortality because of infection with acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus causes disease 2019 (COVID‐19) is a race against clock virus. Here we describe an amphiphilic imidazoquinoline (IMDQ‐PEG‐CHOL) TLR7/8 adjuvant, consisting conjugated to chain end cholesterol‐poly(ethylene glycol) macromolecular amphiphile. It water‐soluble exhibits massive translocation lymph nodes upon local administration through binding albumin, affording localized innate immune activation reduction in systemic inflammation. adjuvanticity IMDQ‐PEG‐CHOL was validated licensed vaccine setting (quadrivalent influenza vaccine) experimental trimeric recombinant SARS‐CoV‐2 spike protein vaccine, showing robust IgG2a IgG1 antibody titers mice could neutralize viral vitro vivo mouse model.

Language: Английский

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Mucus-Inspired Dynamic Hydrogels: Synthesis and Future Perspectives

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(44), P. 20137 - 20152

Published: Sept. 8, 2022

Mucus hydrogels at biointerfaces are crucial for protecting against foreign pathogens and the biological functions of underlying cells. Since mucus can bind to host both viruses bacteria, establishing a synthetic model system that emulate properties native be synthesized large scale would revolutionize mucus-related research is essential understanding pathways many infectious diseases. The synthesis such biofunctional in laboratory highly challenging, owing their complex chemical compositions specific interactions occur throughout gel network. In this perspective, we discuss basic structures diverse physicochemical responsible unique hydrogels. We scrutinize different approaches preparing mucus-inspired hydrogels, with examples. also recent what it reveals about challenges must addressed opportunities considered achieve desirable de novo

Language: Английский

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Incidence and management of the main serious adverse events reported after COVID‐19 vaccination

Pharmacology Research & Perspectives, Journal Year: 2024, Volume and Issue: 12(3)

Published: June 1, 2024

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China 2019. Soon after, it was declared a pandemic World Health Organization. The health crisis imposed new virus and its rapid spread worldwide prompted fast development of vaccines. For time human history, two vaccines based on recombinant genetic material technology were approved for use. These mRNA applied massive immunization programs around world, followed other more traditional approaches. Even though all tested clinical trials prior to their general administration, serious adverse events, usually very low incidence, mostly identified after application millions doses. Establishing direct correlation (the cause-effect paradigm) between vaccination appearance effects has proven challenging. This review focuses main observed vaccination, including anaphylaxis, myocarditis, vaccine-induced thrombotic thrombocytopenia, Guillain-Barré syndrome, transverse myelitis reported context COVID-19 vaccination. We highlight symptoms, laboratory tests required an adequate diagnosis, briefly outline recommended treatments these effects. aim this work is increase awareness among healthcare personnel about events that may arise post-vaccination. Regardless ongoing discussion safety must be promptly treated effectively reduce risk complications.

Language: Английский

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Current Status of COVID‐19 (Pre)Clinical Vaccine Development

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(43), P. 18885 - 18897

Published: July 14, 2020

Abstract The current COVID‐19 pandemic has a tremendous impact on daily life world‐wide. Despite the ability to dampen spread of SARS‐CoV‐2, causative agent diseases, through restrictive interventions, it is believed that only effective vaccines will provide sufficient control over disease and revert societal live back normal. At present, double‐digit number efforts are devoted development vaccine against COVID‐19. Here, we an overview these (pre)clinical background information technologies behind vaccines. In addition, discuss potential hurdles need be addressed prior mass scale clinical translation successful candidates.

Language: Английский

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Severe acute respiratory syndrome‐coronavirus‐2 spike (S) protein based vaccine candidates: State of the art and future prospects

Reviews in Medical Virology, Journal Year: 2020, Volume and Issue: 31(3)

Published: Oct. 15, 2020

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) which responsible for a global pandemic that started in late Wuhan, China. To prevent the worldwide spread of this highly pathogenic virus, development an effective and safe vaccine urgently needed. The SARS-CoV-2 SARS-CoV share high degree genetic pathologic identity safety immune-enhancement concerns regarding development. Prior animal studies with first generation (whole virus-based) preparations vaccines (inactivated attenuated modalities) indicated possibility increased infectivity or eosinophilic infiltration immunization. Therefore, second third safer (by using modern platforms) actively sought viral infection. spike (S) protein SARS-CoVs main determinant cell entry tropism facilitating zoonosis into humans sustained person-to-person transmission. Furthermore, 'S' contains multiple neutralizing epitopes play essential role induction antibodies (nAbs) protective immunity. Moreover, T-cell responses against have also been characterized correlate to IgG IgA antibody titres Covid-19 patients. Thus, S obvious candidate antigen inclusion platforms This manuscript reviews different characteristics protein, its potency 'state art' strategies antigen, construction vaccine.

Language: Английский

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Quality by design modelling to support rapid RNA vaccine production against emerging infectious diseases

npj Vaccines, Journal Year: 2021, Volume and Issue: 6(1)

Published: April 29, 2021

Abstract Rapid-response vaccine production platform technologies, including RNA vaccines, are being developed to combat viral epidemics and pandemics. A key enabler of rapid response is having quality-oriented disease-agnostic manufacturing protocols ready ahead outbreaks. We the first apply Quality by Design (QbD) framework enhance rapid-response against known future pathogens. This QbD aims support development consistent safe efficacious integrating a novel qualitative methodology quantitative bioprocess model. The identifies assesses direction, magnitude shape impact critical process parameters (CPPs) on quality attributes (CQAs). mechanistic model quantifies maps effect four CPPs CQA effective yield drug substance. Consequently, design space an synthesis bioreactor obtained. cost-yield optimization together with probabilistic contribute towards automation rapid-response, high-quality production.

Language: Английский

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Perspectives in Peptide-Based Vaccination Strategies for Syndrome Coronavirus 2 Pandemic

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: Dec. 3, 2020

At the end of December 2019, an epidemic form respiratory tract infection now named COVID-19 emerged in Wuhan, China. It is caused by a newly identified viral pathogen, severe acute syndrome coronavirus (SARS-CoV-2), which can cause pneumonia and distress syndrome. On January 30, 2020, due to rapid spread infection, was declared as global health emergency World Health Organization. Coronaviruses are enveloped RNA viruses belonging family Coronaviridae, able infect birds, humans other mammals. The majority human infections mild although already 2003 2012, epidemics SARS-CoV Middle East Respiratory Syndrome (MERS-CoV), respectively, were characterized high mortality rate. In this regard, many efforts have been made develop therapeutic strategies against CoV but, unfortunately, drug candidates shown efficacy only into vitro studies, limiting their use infection. Actually, no treatment has approved SARS-CoV-2, therefore there urgent need suitable vaccine tackle issue. However, puzzled scenario biological features virus its interaction with immune response, represent challenge for development. As expected, hundreds research laboratories running out breath explore different obtain safe quickly spreadable vaccine; among others, peptide-based approach represents turning point peptides demonstrated unique selectivity specificity toward specific targets. Peptide-based vaccines imply identification epitopes both on cells capsid design peptide/peptidomimetics counteract primary host-pathogen interaction, order induce host response. SARS-CoV-2 immunogenic regions mainly distributed, well coronaviruses, across structural areas such spike, envelope, membrane or nucleocapsid proteins. Herein, we aim highlight molecular basis recent fight pandemic including delivery systems.

Language: Английский

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