scholarly journals Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

2021 ◽  
Author(s):  
Marie I. Samanovic ◽  
Amber R. Cornelius ◽  
Sophie L. Gray-Gaillard ◽  
Joseph Richard Allen ◽  
Trishala Karmacharya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Prior History ◽  
Vaccine Candidates ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
Efficacy Trials ◽  
History Of ◽  
Humoral Responses

ABSTRACTThe use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.

scholarly journals Baseline Levels of Influenza-Specific B Cells and T Cell Responses Modulate Human Immune Responses to Swine Variant Influenza A/H3N2 Vaccine

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 126
Author(s):  
Lilin Lai ◽  
Nadine Rouphael ◽  
Yongxian Xu ◽  
Amy C. Sherman ◽  
Srilatha Edupuganti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A ◽  
Vaccine Dose ◽  
T Cell Responses ◽  
Post Vaccination ◽  
Cell Responses ◽  
Cellular Immune Responses ◽  
Cellular Immune

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses.

scholarly journals Induction of Specific T-Cell Responses, Opsonizing Antibodies, and Protection against Plasmodium chabaudi adami Infection in Mice Vaccinated with Genomic Expression Libraries Expressed in Targeted and Secretory DNA Vectors

2003 ◽  
Vol 71 (8) ◽  
pp. 4506-4515 ◽  
Author(s):  
A. Rainczuk ◽  
T. Scorza ◽  
P. M. Smooker ◽  
T. W. Spithill
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Genomic Library ◽  
Protective Efficacy ◽  
T Cell Responses ◽  
Interleukin 4 ◽  
Plasmodium Chabaudi ◽  
Lethal Challenge ◽  
Cell Responses ◽  
Expression Libraries

ABSTRACT It has been proposed that a multivalent malaria vaccine is necessary to mimic the naturally acquired resistance to this disease observed in humans. A major experimental challenge is to identify the optimal components to be used in such a multivalent vaccine. Expression library immunization (ELI) is a method for screening genomes of a pathogen to identify novel combinations of vaccine sequences. Here we describe immune responses associated with, and the protective efficacy of, genomic Plasmodium chabaudi adami DS expression libraries constructed in VR1020 (secretory), monocyte chemotactic protein-3 (chemoattractant), and cytotoxic T lymphocyte antigen 4 (lymph node-targeting) DNA vaccine vectors. With splenocytes from vaccinated mice, specific T-cell responses, as well as gamma interferon and interleukin-4 production, were observed after stimulation with P. chabaudi adami-infected erythrocytes, demonstrating the specificity of genomic library vaccination for two of the three libraries constructed. Sera obtained from mice vaccinated with genomic libraries promoted the opsonization of P. chabaudi adami-infected erythrocytes by murine macrophages in vitro, further demonstrating the induction of malaria-specific immune responses following ELI. Over three vaccine trials using biolistic delivery of the three libraries, protection after lethal challenge with P. chabaudi adami DS ranged from 33 to 50%. These results show that protective epitopes or antigens are expressed within the libraries and that ELI induces responses specific to P. chabaudi adami malaria. This study further demonstrates that ELI is a suitable approach for screening the malaria genome to identify the components of multivalent vaccines.

scholarly journals Differential CD4+ versus CD8+ T-Cell Responses Elicited by Different Poxvirus-Based Human Immunodeficiency Virus Type 1 Vaccine Candidates Provide Comparable Efficacies in Primates

2008 ◽  
Vol 82 (6) ◽  
pp. 2975-2988 ◽  
Author(s):  
Petra Mooij ◽  
Sunita S. Balla-Jhagjhoorsingh ◽  
Gerrit Koopman ◽  
Niels Beenhakker ◽  
Patricia van Haaften ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Immune Responses ◽  
Vaccinia Virus ◽  
T Cell Responses ◽  
Vaccine Candidates ◽  
Cell Responses ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Poxvirus vectors have proven to be highly effective for boosting immune responses in diverse vaccine settings. Recent reports reveal marked differences in the gene expression of human dendritic cells infected with two leading poxvirus-based human immunodeficiency virus (HIV) vaccine candidates, New York vaccinia virus (NYVAC) and modified vaccinia virus Ankara (MVA). To understand how complex genomic changes in these two vaccine vectors translate into antigen-specific systemic immune responses, we undertook a head-to-head vaccine immunogenicity and efficacy study in the pathogenic HIV type 1 (HIV-1) model of AIDS in Indian rhesus macaques. Differences in the immune responses in outbred animals were not distinguished by enzyme-linked immunospot assays, but differences were distinguished by multiparameter fluorescence-activated cell sorter analysis, revealing a difference between the number of animals with both CD4+ and CD8+ T-cell responses to vaccine inserts (MVA) and those that elicit a dominant CD4+ T-cell response (NYVAC). Remarkably, vector-induced differences in CD4+/CD8+ T-cell immune responses persisted for more than a year after challenge and even accompanied antigenic modulation throughout the control of chronic infection. Importantly, strong preexposure HIV-1/simian immunodeficiency virus-specific CD4+ T-cell responses did not prove deleterious with respect to accelerated disease progression. In contrast, in this setting, animals with strong vaccine-induced polyfunctional CD4+ T-cell responses showed efficacies similar to those with stronger CD8+ T-cell responses.

scholarly journals Protective efficacy of an orf virus-vector encoding the hemmagglutinin and the nucleoprotein of influenza A virus in swine

2021 ◽  
Author(s):  
Lok R. Joshi ◽  
David Knudsen ◽  
Pablo Pineyro ◽  
Santhosh Dhakal ◽  
Gourapura J. Renukaradhya ◽  
...  
Keyword(s):  
Viral Load ◽  
T Cell ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Protective Efficacy ◽  
Swine Influenza ◽  
Virus Shedding ◽  
Recombinant Viruses ◽  
Cell Responses

AbstractSwine influenza is a highly contagious respiratory disease of pigs caused by influenza A viruses (IAV-S). IAV-S causes significant economic losses to the swine industry and poses constant challenges to public health due to its zoonotic potential. Thus effective IAV-S vaccines are highly desirable and would benefit both animal and human health. Here, we developed two recombinant orf viruses, expressing the hemagglutinin (HA) gene (OV-HA) or both the HA and the nucleoprotein (NP) genes of IAV-S (OV-HA-NP). The immunogenicity and protective efficacy of these two recombinant viruses were evaluated in pigs. Both OV-HA and OV-HA-NP recombinants elicited robust virus neutralizing antibody response in pigs. Notably, although both recombinant viruses elicited IAV-S-specific T-cell responses, the frequency of IAV-S specific proliferating T cells secreting IFN-γ upon re-stimulation was higher in OV-HA-NP-immunized animals than in the OV-HA group. Importantly, IgG1/IgG2 isotype ELISAs revealed that immunization with OV-HA induced Th2-biased immune responses, whereas immunization with OV-HA-NP virus resulted in a Th1-biased immune response. While pigs immunized with either OV-HA or OV-HA-NP were protected when compared to non-immunized controls, immunization with OV-HA-NP resulted in better protective efficacy as evidenced by reduced virus shedding in nasal secretions and reduced viral load in the lung. This study demonstrates the potential of ORFV-based vector for control of swine influenza virus in swine.ImportanceEffective influenza A virus (IAV-S) vaccines capable of providing robust protection to genetically diverse IAV-S in swine are lacking. Here, we explored the potential of orf virus based vectors expressing the hemagglutining (HA) or both the HA and the nucleoprotein (NP) genes of influena A virus (IAV-S) in eliciting protection against IAV-S in pigs. We observed that both recombinant viruses elicited IAV-S-specific humoral and cell-mediated immune responses in pigs. Addition of the NP and co-expression of this protein with HA, another major influenza protective antigen, resulted in higher T cell responses which presumably led to better protection in OV-HA-NP immunized animals, as evidenced by lower levels of virus shedding and viral load in lungs. This study highlights the the potential of ORFV as a vector platform for vaccine delivery against IAV-S. Results here provide the foundation for future development of broadly protective ORFV-based vectors for IAV-S for use in swine.

scholarly journals Past SARS-CoV-2 infection elicits a strong immune response after a single vaccine dose

2021 ◽  
Author(s):  
Rossana Elena Chahla ◽  
Rodrigo Hernan Tomas-Grau ◽  
Silvia Ines Cazorla ◽  
Diego Ploper ◽  
Esteban Vera Pingitore ◽  
...  
Keyword(s):  
Immune Response ◽  
Health Personnel ◽  
Vaccine Dose ◽  
Antibody Responses ◽  
Control Group ◽  
Prior History ◽  
Secondary Antibody ◽  
Strong Immune Response ◽  
History Of Disease ◽  
History Of

We hypothesized that in individuals with previous SARS-CoV-2 infection, the first vaccine dose would work as a booster, eliciting a faster and more intense immune response. We herein describe antibody responses to the first and second doses of Gam-COVID-Vac (SPUTNIK V) vaccine in health personnel of Tucuman, Argentina, with previous COVID-19 and compared it with uninfected personnel. Individuals with anti-SARS-CoV-2 titers at baseline showed significantly higher responses to the first dose than people with no prior history of disease (p <0.0001), with titers higher to those registered after the second dose in the control group, representing a clear secondary antibody response. This suggests that a single dose of SPUTNIK V for people with previous SARS-CoV-2 infection could contribute to a better use of available doses.

scholarly journals Humoral and cellular responses to mRNA vaccines against SARS-CoV2 in patients with a history of CD20-B-cell depleting therapy

2021 ◽  
Author(s):  
Matthias B. Moor ◽  
Franziska Suter-Riniker ◽  
Michael P. Horn ◽  
Daniel Aeberli ◽  
Jennifer Amsler ◽  
...  
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Vaccine Dose ◽  
Lymphocyte Subpopulation ◽  
University Hospital ◽  
Healthy Controls ◽  
Vaccine Response ◽  
Treatment History ◽  
History Of ◽  
Anti Cd20

Background B-cell depleting therapies increase COVID19 morbidity and mortality. For this specific population, evidence-based vaccination strategies are lacking. Here, we investigated humoral and cell mediated immune responses to SARS-CoV2 mRNA-based vaccines in patients receiving CD20-B-cell depleting agents for autoimmune disease, malignancy, or transplantation. Methods Patients at the Bern University Hospital with a treatment history of anti-CD20 depleting agents (rituximab or ocrelizumab) were enrolled for analysis of humoral and cell-mediated immune responses (by IFN-g release assay) after completing vaccination against SARS-CoV2. Primary outcome was the the anti-spike antibody response in anti-CD20-treated patients (n=96) in comparison to immunocompetent controls (n=29). Results Anti-spike IgG antibodies were detected in 49% of patients 1.79 months after the second vaccine dose (interquartile range, IQR: 1.16-2.48) compared to 100% of controls (p<0.001). SARS-CoV2 specific interferon-g; release was detected in 17% of patients and 86% of healthy controls (p<0.001). Only 5% of patients, but 86% of healthy controls showed positive reactions in both assays, respectively (p<0.001). Time since last anti-CD20 therapy (7.6 months), peripheral CD19+ (>27/ul), and CD4+ lymphocyte count (>653/ul) predicted humoral vaccine response (area under the curve [AUC]: 62% [CI 56-78], 67% [CI 58-80] and 67% [CI 54-79], (positive predictive value [PPV]: 0.76, 0.7 and 0.71). Conclusion This study provides evidence for blunted humoral and cell-mediated immune responses elicited by SARS-CoV2 mRNA vaccines in patients with CD20-depleting treatment history. Lymphocyte subpopulation counts are associated with vaccine response in this highly vulnerable population. (Funded by Bern University Hospital, ClinicalTrials.gov number, NCT04877496)

scholarly journals African Green Monkeys Recapitulate the Clinical Experience with Replication of Live Attenuated Pandemic Influenza Virus Vaccine Candidates

2014 ◽  
Vol 88 (14) ◽  
pp. 8139-8152 ◽  
Author(s):  
Yumiko Matsuoka ◽  
Amorsolo Suguitan ◽  
Marlene Orandle ◽  
Myeisha Paskel ◽  
Kobporn Boonnak ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Animal Models ◽  
Avian Influenza ◽  
Immune Responses ◽  
Respiratory Tract ◽  
Nonhuman Primate ◽  
Protective Efficacy ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Green Monkeys

ABSTRACTLive attenuated cold-adapted (ca) H5N1, H7N3, H6N1, and H9N2 influenza vaccine viruses replicated in the respiratory tract of mice and ferrets, and 2 doses of vaccines were immunogenic and protected these animals from challenge infection with homologous and heterologous wild-type (wt) viruses of the corresponding subtypes. However, when these vaccine candidates were evaluated in phase I clinical trials, there were inconsistencies between the observations in animal models and in humans. The vaccine viruses did not replicate well and immune responses were variable in humans, even though the study subjects were seronegative with respect to the vaccine viruses before vaccination. Therefore, we sought a model that would better reflect the findings in humans and evaluated African green monkeys (AGMs) as a nonhuman primate model. The distribution of sialic acid (SA) receptors in the respiratory tract of AGMs was similar to that in humans. We evaluated the replication ofwtandcaviruses of avian influenza (AI) virus subtypes H5N1, H6N1, H7N3, and H9N2 in the respiratory tract of AGMs. All of thewtviruses replicated efficiently, while replication of thecavaccine viruses was restricted to the upper respiratory tract. Interestingly, the patterns and sites of virus replication differed among the different subtypes. We also evaluated the immunogenicity and protective efficacy of H5N1, H6N1, H7N3, and H9N2cavaccines. Protection fromwtvirus challenge correlated well with the level of serum neutralizing antibodies. Immune responses were slightly better when vaccine was delivered by both intranasal and intratracheal delivery than when it was delivered intranasally by sprayer. We conclude that live attenuated pandemic influenza virus vaccines replicate similarly in AGMs and human subjects and that AGMs may be a useful model to evaluate the replication ofcavaccine candidates.IMPORTANCEFerrets and mice are commonly used for preclinical evaluation of influenza vaccines. However, we observed significant inconsistencies between observations in humans and in these animal models. We used African green monkeys (AGMs) as a nonhuman primate (NHP) model for a comprehensive and comparative evaluation of pairs of wild-type and pandemic live attenuated influenza virus vaccines (pLAIV) representing four subtypes of avian influenza viruses and found that pLAIVs replicate similarly in AGMs and humans and that AGMs can be useful for evaluation of the protective efficacy of pLAIV.

scholarly journals Comparison of Memory B Cell, Antibody-Secreting Cell, and Plasma Antibody Responses in Young Children, Older Children, and Adults with Infection Caused by Vibrio cholerae O1 El Tor Ogawa in Bangladesh

2011 ◽  
Vol 18 (8) ◽  
pp. 1317-1325 ◽  
Author(s):  
Daniel T. Leung ◽  
Mohammad Arif Rahman ◽  
M. Mohasin ◽  
M. Asrafuzzaman Riyadh ◽  
Sweta M. Patel ◽  
...  
Keyword(s):  
Young Children ◽  
Immune Responses ◽  
B Cell ◽  
Protective Efficacy ◽  
Age Groups ◽  
Older Children ◽  
Secreting Cell ◽  
Content Type ◽  
Antibody Secreting Cell ◽  
Plasma Antibody

ABSTRACTChildren bear a large component of the global burden of cholera. Despite this, little is known about immune responses to cholera in children, especially those under 5 years of age. Cholera vaccine studies have demonstrated lower long-term protective efficacy in young children than in older children and adults. Memory B cell (MBC) responses may correlate with duration of protection following infection and vaccination. Here we report a comparison of immune responses in young children (3 to 5 years of age;n= 17), older children (6 to 17 years of age;n= 17), and adults (18 to 60 years of age;n= 68) hospitalized with cholera in Dhaka, Bangladesh. We found that young children had lower baseline vibriocidal antibody titers and higher fold increases in titer between day 2 and day 7 than adults. Young children had higher baseline IgG plasma antibody levels toVibrio choleraeantigens, although the magnitudes of responses at days 7 and 30 were similar across age groups. As a surrogate marker for mucosal immune responses, we assessed day 7 antibody-secreting cell (ASC) responses. These were comparable across age groups, although there was a trend for older age groups to have higher levels of lipopolysaccharide-specific IgA ASC responses. All age groups developed comparable MBC responses toV. choleraelipopolysaccharide and cholera toxin B subunit at day 30. These findings suggest that young children are able to mount robust vibriocidal, plasma antibody, ASC, and MBC responses againstV. choleraeO1, suggesting that under an optimal vaccination strategy, young children could achieve protective efficacy comparable to that induced in adults.

scholarly journals Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

2017 ◽  
Vol 91 (24) ◽  
Author(s):  
Donald M. Carter ◽  
Christopher A. Darby ◽  
Scott K. Johnson ◽  
Michael A. Carlock ◽  
Greg A. Kirchenbaum ◽  
...  
Keyword(s):  
Animal Models ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Animal Studies ◽  
Protective Efficacy ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Vaccine Candidates ◽  
Naive Animal

ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long-lasting protective immune responses. The goal of these vaccines is to stimulate immune responses that react against most, if not all, circulating influenza strains, over a long period of time in all populations of people. Commonly, these experimental vaccines are tested in naive animal models that do not have anti-influenza immune responses; however, humans have preexisting immunity to influenza viral antigens, particularly antibodies to the HA and NA glycoproteins. Therefore, this study investigated how preexisting antibodies to historical influenza viruses influenced HAI-specific antibodies and protective efficacy using a broadly protective vaccine candidate.

scholarly journals The Search of a Malaria Vaccine: The Time for Modified Immuno-Potentiating Probes

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 115 ◽  
Author(s):  
José Manuel Lozano ◽  
Zully Rodríguez Parra ◽  
Salvador Hernández-Martínez ◽  
Maria Fernanda Yasnot-Acosta ◽  
Angela Patricia Rojas ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Protective Efficacy ◽  
Rodent Models ◽  
African Countries ◽  
Vaccine Candidates ◽  
Efficacy Trials ◽  
Limited Efficacy ◽  
Urgent Task ◽  
Human Sera ◽  
Chemical Strategies

Malaria is a deadly disease that takes the lives of more than 420,000 people a year and is responsible for more than 229 million clinical cases globally. In 2019, 95% of malaria morbidity occurred in African countries. The development of a highly protective vaccine is an urgent task that remains to be solved. Many vaccine candidates have been developed, from the use of the entire attenuated and irradiated pre-erythrocytic parasite forms (or recombinantly expressed antigens thereof) to synthetic candidates formulated in a variety of adjuvants and delivery systems, however these have unfortunately proven a limited efficacy. At present, some vaccine candidates are finishing safety and protective efficacy trials, such as the PfSPZ and the RTS,S/AS01 which are being introduced in Africa. We propose a strategy for introducing non-natural elements into target antigens representing key epitopes of Plasmodium spp. Accordingly, chemical strategies and knowledge of host immunity to Plasmodium spp. have served as the basis. Evidence is obtained after being tested in experimental rodent models for malaria infection and recognized for human sera from malaria-endemic regions. This encourages us to propose such an immune-potentiating strategy to be further considered in the search for new vaccine candidates.

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