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1.
JCI Insight ; 6(24)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1598468

ABSTRACT

mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.


Subject(s)
/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , /therapeutic use , Adaptive Immunity/genetics , Adaptive Immunity/immunology , Adult , Aged , Antigens, Viral , B-Lymphocytes , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , COVID-19/prevention & control , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carrier State , Convalescence , Epitopes , Female , Humans , Immunity, Cellular/genetics , Immunity, Humoral/genetics , Immunogenicity, Vaccine , Immunologic Memory , Male , Middle Aged , RNA-Seq , SARS-CoV-2 , Single-Cell Analysis , Spike Glycoprotein, Coronavirus/immunology , Th1 Cells , Th17 Cells , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Young Adult , /therapeutic use
2.
Nat Commun ; 12(1): 6222, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1493103

ABSTRACT

The importance of breastmilk in postnatal life lies in the strong association between breastfeeding and the reduction in the risk of infection and infection-related infant mortality. However, data regarding the induction and dynamics of breastmilk antibodies following administration of the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine is scarce, as pregnant and lactating women were not included in the initial vaccine clinical trials. Here, we investigate the dynamics of the vaccine-specific antibody response in breastmilk and serum in a prospective cohort of ten lactating women who received two doses of the mRNA vaccine. We show that the antibody response is rapid and highly synchronized between breastmilk and serum, reaching stabilization 14 days after the second dose. The response in breastmilk includes both IgG and IgA with neutralization capacity.


Subject(s)
Breast Feeding , COVID-19 Vaccines/genetics , RNA, Messenger/blood , Adult , Animals , Antibody Formation/genetics , Antibody Formation/physiology , Female , Humans , Milk/chemistry , RNA, Messenger/analysis , Vaccines, Synthetic/therapeutic use
3.
Pediatr Clin North Am ; 68(5): 961-976, 2021 10.
Article in English | MEDLINE | ID: covidwho-1428320

ABSTRACT

Children usually present with milder symptoms of COVID-19 as compared with adults. Supportive care alone is appropriate for most children with COVID-19. Antiviral therapy may be required for those with severe or critical diseases. Currently there has been a rapid development of vaccines globally to prevent COVID-19 and several vaccines are being evaluated in children and adolescents. Currently, only the Pfizer-BioNTech messenger RNA vaccine is approved for emergency authorization use in the pediatric population ages 16 years and older.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Systemic Inflammatory Response Syndrome/prevention & control , Vaccines, Synthetic/therapeutic use , Adolescent , Child , Humans , Safety , Vaccines, Synthetic/adverse effects
5.
Biochem Soc Trans ; 49(5): 2411-2429, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1397910

ABSTRACT

The importance of vaccine-induced protection was repeatedly demonstrated over the last three decades and emphasized during the recent COVID-19 pandemic as the safest and most effective way of preventing infectious diseases. Vaccines have controlled, and in some cases, eradicated global viral and bacterial infections with high efficiency and at a relatively low cost. Carbohydrates form the capsular sugar coat that surrounds the outer surface of human pathogenic bacteria. Specific surface-exposed bacterial carbohydrates serve as potent vaccine targets that broadened our toolbox against bacterial infections. Since first approved for commercial use, antibacterial carbohydrate-based vaccines mostly rely on inherently complex and heterogenous naturally derived polysaccharides, challenging to obtain in a pure, safe, and cost-effective manner. The introduction of synthetic fragments identical with bacterial capsular polysaccharides provided well-defined and homogenous structures that resolved many challenges of purified polysaccharides. The success of semisynthetic glycoconjugate vaccines against bacterial infections, now in different phases of clinical trials, opened up new possibilities and encouraged further development towards fully synthetic antibacterial vaccine solutions. In this mini-review, we describe the recent achievements in semi- and fully synthetic carbohydrate vaccines against a range of human pathogenic bacteria, focusing on preclinical and clinical studies.


Subject(s)
Anti-Bacterial Agents/immunology , Bacteria/immunology , Bacterial Infections/immunology , Carbohydrates/immunology , Glycoconjugates/immunology , Vaccines, Synthetic/immunology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Carbohydrate Sequence , Carbohydrates/chemistry , Glycoconjugates/chemistry , Glycoconjugates/therapeutic use , Humans , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/therapeutic use
7.
Cell ; 184(6): 1589-1603, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1141229

ABSTRACT

Vaccines are critical tools for maintaining global health. Traditional vaccine technologies have been used across a wide range of bacterial and viral pathogens, yet there are a number of examples where they have not been successful, such as for persistent infections, rapidly evolving pathogens with high sequence variability, complex viral antigens, and emerging pathogens. Novel technologies such as nucleic acid and viral vector vaccines offer the potential to revolutionize vaccine development as they are well-suited to address existing technology limitations. In this review, we discuss the current state of RNA vaccines, recombinant adenovirus vector-based vaccines, and advances from biomaterials and engineering that address these important public health challenges.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Adenoviridae/genetics , Animals , Antigens, Viral/genetics , Biocompatible Materials , COVID-19/virology , Drug Delivery Systems/methods , Genetic Vectors/immunology , Humans , Immunogenicity, Vaccine , Liposomes , Nanoparticles , RNA, Messenger/chemical synthesis , RNA, Messenger/immunology
8.
Front Immunol ; 12: 679344, 2021.
Article in English | MEDLINE | ID: covidwho-1325528

ABSTRACT

Recently, mRNA vaccines have become a significant type of therapeutic and have created new fields in the biopharmaceutical industry. mRNA vaccines are promising next-generation vaccines that have introduced a new age in vaccinology. The recent approval of two COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) has accelerated mRNA vaccine technology and boosted the pharmaceutical and biotechnology industry. These mRNA vaccines will help to tackle COVID-19 pandemic through immunization, offering considerable hope for future mRNA vaccines. Human trials with data both from mRNA cancer vaccines and mRNA infectious disease vaccines have provided encouraging results, inspiring the pharmaceutical and biotechnology industries to focus on this area of research. In this article, we discuss current mRNA vaccines broadly in two parts. In the first part, mRNA vaccines in general and COVID-19 mRNA vaccines are discussed. We presented the mRNA vaccine structure in general, the different delivery systems, the immune response, and the recent clinical trials for mRNA vaccines (both for cancer mRNA vaccines and different infectious diseases mRNA vaccines). In the second part, different COVID-19 mRNA vaccines are explained. Finally, we illustrated a snapshot of the different leading mRNA vaccine developers, challenges, and future prospects of mRNA vaccines.


Subject(s)
COVID-19 Vaccines/therapeutic use , Cancer Vaccines/therapeutic use , Drug Development , Vaccines, Synthetic/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/genetics , COVID-19 Vaccines/immunology , Cancer Vaccines/genetics , Cancer Vaccines/immunology , Dendritic Cells/immunology , Drug Delivery Systems , Humans , Immunity , Neoplasms/immunology , Neoplasms/therapy , SARS-CoV-2/immunology , Vaccination , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
9.
Signal Transduct Target Ther ; 6(1): 213, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249203

ABSTRACT

Although inoculation of COVID-19 vaccines has rolled out globally, there is still a critical need for safe and effective vaccines to ensure fair and equitable supply for all countries. Here, we report on the development of a highly efficacious mRNA vaccine, SW0123 that is composed of sequence-modified mRNA encoding the full-length SARS-CoV-2 Spike protein packaged in core-shell structured lipopolyplex (LPP) nanoparticles. SW0123 is easy to produce using a large-scale microfluidics-based apparatus. The unique core-shell structured nanoparticle facilitates vaccine uptake and demonstrates a high colloidal stability, and a desirable biodistribution pattern with low liver targeting effect upon intramuscular administration. Extensive evaluations in mice and nonhuman primates revealed strong immunogenicity of SW0123, represented by induction of Th1-polarized T cell responses and high levels of antibodies that were capable of neutralizing not only the wild-type SARS-CoV-2, but also a panel of variants including D614G and N501Y variants. In addition, SW0123 conferred effective protection in both mice and non-human primates upon SARS-CoV-2 challenge. Taken together, SW0123 is a promising vaccine candidate that holds prospects for further evaluation in humans.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/virology , COVID-19 Vaccines/therapeutic use , Female , Humans , Immunogenicity, Vaccine/immunology , Lymphocyte Activation/immunology , Mice , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Th1 Cells/immunology , Th1 Cells/virology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Viral Vaccines/immunology
10.
Chem Res Toxicol ; 34(8): 1823-1825, 2021 08 16.
Article in English | MEDLINE | ID: covidwho-1233682

ABSTRACT

SARS-CoV-2 has infected more than 100 million people, causing 2 million deaths globally. Studies on the development of a vaccine ended up with different formulations. We herein discuss the safety record of the two approved vaccines.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , Humans , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use
11.
Medicina (Kaunas) ; 57(3)2021 Mar 09.
Article in English | MEDLINE | ID: covidwho-1167649

ABSTRACT

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Adjuvants, Immunologic/adverse effects , Autoimmune Diseases/chemically induced , Drug Approval , Drug Evaluation, Preclinical , Hippocratic Oath , Humans , Long Term Adverse Effects/chemically induced , Models, Animal , Risk Assessment , SARS-CoV-2 , Vaccines, Inactivated/therapeutic use , Vaccines, Synthetic/therapeutic use
12.
Front Immunol ; 12: 657711, 2021.
Article in English | MEDLINE | ID: covidwho-1156127

ABSTRACT

Background: BNT162b2 and mRNA-1273 are the two recently approved mRNA-based vaccines against COVID-19 which has shown excellent safety and efficacy. Preliminary data about specific and neutralizing antibodies is available covering the first 100 days after vaccination. Methods: We reviewed all the publications regarding the immunologic consequences of BNT162b2 and mRNA-1273 vaccination. A summary of specific antibodies concentration and neutralizing antibodies titers elicited by each vaccine is provided. Results: BNT162b2 and mRNA-1273 displayed a reassuring safety and efficacy profile, with the latter above 94%. They can elicit specific antibodies titers and neutralizing antibodies concentrations that are far superior from those observed among COVID-19 human convalescent serum, across a wide span of age, for at least 100 days after vaccination. Moreover, the vaccine-induced T cellular response is oriented toward a TH1 response and no evidence of vaccine-enhanced disease have been reported. Discussion: BNT162b2 and mRNA-1273 can elicit specific antibodies titers and neutralizing antibodies concentrations above those observed among COVID-19 human convalescent serum in the first 100 days after vaccination. Data about vaccine efficacy in those with previous COVID-19 or immunocompromised is still limited.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Immunization , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Vaccines, Synthetic/therapeutic use , Animals , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/blood , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/adverse effects , Diffusion of Innovation , Host-Pathogen Interactions , Humans , SARS-CoV-2/genetics , Treatment Outcome , Vaccines, Synthetic/adverse effects
14.
Pharm Res ; 38(3): 473-478, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1117456

ABSTRACT

The COVID-19 pandemic has left scientists and clinicians no choice but a race to find solutions to save lives while controlling the rapid spreading. Messenger RNA (mRNA)-based vaccines have become the front-runners because of their safety profiles, precise and reproducible immune response with more cost-effective and faster production than other types of vaccines. However, the physicochemical properties of naked mRNA necessitate innovative delivery technologies to ferry these 'messengers' to ribosomes inside cells by crossing various barriers and subsequently induce an immune response. Intracellular delivery followed by endosomal escape represents the key strategies for cytoplasmic delivery of mRNA vaccines to the target. This Perspective provides insights into how state-of-the-art nanotechnology helps break the delivery barriers and advance the development of mRNA vaccines. The challenges remaining and future perspectives are outlined.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Cytoplasm/metabolism , Drug Carriers , Lipids/chemistry , Nanoparticles , Ribosomes/metabolism , Vaccines, Synthetic/therapeutic use , Animals , COVID-19/immunology , COVID-19/virology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/pharmacokinetics , Drug Compounding , Humans , Nanomedicine , Vaccines, Synthetic/chemistry
15.
Mol Cancer ; 20(1): 33, 2021 02 16.
Article in English | MEDLINE | ID: covidwho-1088597

ABSTRACT

mRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.


Subject(s)
Vaccines, Synthetic/therapeutic use , Animals , COVID-19/immunology , Gene Transfer Techniques , Humans , Immunity, Humoral , Immunotherapy , RNA Stability , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology
16.
Cell ; 184(6): 1401, 2021 03 18.
Article in English | MEDLINE | ID: covidwho-1030852

ABSTRACT

The first two vaccines proven to be effective for inhibiting COVID-19 illness were both mRNA, achieving 95% efficacy (and safety) among 74,000 participants (half receiving placebo) after intramuscular delivery of two shots, 3-4 weeks apart. To view this Bench to Bedside, open or download the PDF.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/therapeutic use , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/therapeutic use , Antigen-Presenting Cells/immunology , B-Lymphocytes/immunology , COVID-19/virology , Drug Delivery Systems/methods , Humans , Liposomes , Nanoparticles , Spike Glycoprotein, Coronavirus/immunology , T-Lymphocytes/immunology , Treatment Outcome
18.
Hum Vaccin Immunother ; 16(12): 2905-2912, 2020 12 01.
Article in English | MEDLINE | ID: covidwho-970085

ABSTRACT

SARS-CoV-2, the causative agent of COVID-19, has imposed a major public health threat, which needs effective therapeutics and vaccination strategies. Several potential candidate vaccines being rapidly developed are in clinical evaluation. Considering the crucial role of SARS-CoV-2 spike (S) glycoprotein in virus attachment, entry, and induction of neutralizing antibodies, S protein is being widely used as a target for vaccine development. Based on advances in techniques for vaccine design, inactivated, live-vectored, nucleic acid, and recombinant COVID-19 vaccines are being developed and tested for their efficacy. Phase3 clinical trials are underway or will soon begin for several of these vaccines. Assuming that clinical efficacy is shown for one or more vaccines, safety is a major aspect to be considered before deploying such vaccines to the public. The current review focuses on the recent advances in recombinant COVID-19 vaccine research and development and associated issues.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Vaccines, Synthetic/therapeutic use , COVID-19/genetics , COVID-19/metabolism , COVID-19 Vaccines/genetics , COVID-19 Vaccines/metabolism , Genetic Vectors/genetics , Genetic Vectors/metabolism , Genetic Vectors/therapeutic use , Humans , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Vaccines, Synthetic/metabolism
19.
Pediatr Allergy Immunol ; 32(1): 9-16, 2021 01.
Article in English | MEDLINE | ID: covidwho-894789

ABSTRACT

Tremendous efforts are undertaken to quickly develop COVID-19 vaccines that protect vulnerable individuals from severe disease and thereby limit the health and socioeconomic impacts of the pandemic. Potential candidates are tested in adult populations, and questions arise of whether COVID-19 vaccination should be implemented in children. Compared to adults, the incidence and disease severity of COVID-19 are low in children, and despite their infectiveness, their role in disease propagation is limited. Therefore, COVID-19 vaccines will need to have fully demonstrated safety and efficacy in preventing not only complications but transmission to justify childhood vaccination. This work summarizes currently tested vaccine platforms and debates practical and ethical considerations for their potential use in children. It also discusses the already deleterious effect of the pandemic on routine childhood vaccine coverage, calling for action to limit the risks for a rise in vaccine-preventable diseases.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Vaccination/methods , Adolescent , COVID-19 Vaccines/adverse effects , Child , Child, Preschool , Humans , Infant , Pandemics/prevention & control , Risk Factors , SARS-CoV-2/immunology , Vaccination/ethics , Vaccines, DNA/therapeutic use , Vaccines, Synthetic/therapeutic use
20.
Nat Med ; 26(11): 1694-1700, 2020 11.
Article in English | MEDLINE | ID: covidwho-744383

ABSTRACT

Coronavirus disease 2019 (COVID-19) in humans is often a clinically mild illness, but some individuals develop severe pneumonia, respiratory failure and death1-4. Studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hamsters5-7 and nonhuman primates8-10 have generally reported mild clinical disease, and preclinical SARS-CoV-2 vaccine studies have demonstrated reduction of viral replication in the upper and lower respiratory tracts in nonhuman primates11-13. Here we show that high-dose intranasal SARS-CoV-2 infection in hamsters results in severe clinical disease, including high levels of virus replication in tissues, extensive pneumonia, weight loss and mortality in a subset of animals. A single immunization with an adenovirus serotype 26 vector-based vaccine expressing a stabilized SARS-CoV-2 spike protein elicited binding and neutralizing antibody responses and protected against SARS-CoV-2-induced weight loss, pneumonia and mortality. These data demonstrate vaccine protection against SARS-CoV-2 clinical disease. This model should prove useful for preclinical studies of SARS-CoV-2 vaccines, therapeutics and pathogenesis.


Subject(s)
Adenoviridae/genetics , COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology , Adenoviridae/immunology , Animals , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/therapeutic use , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , COVID-19 Vaccines/genetics , Cricetinae , Disease Models, Animal , Female , Genetic Vectors , Humans , Male , Mesocricetus , SARS-CoV-2/genetics , Severity of Illness Index , Vaccines, Synthetic/genetics , Vaccines, Synthetic/therapeutic use , Viral Load
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