Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations

Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune...

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Main Authors: Gabriela Tapia-Calle, Maaike Stoel, Jacqueline de Vries-Idema, Anke Huckriede
Format: Article
Language:English
Published: MDPI AG 2017-08-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/5/3/21
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author Gabriela Tapia-Calle
Maaike Stoel
Jacqueline de Vries-Idema
Anke Huckriede
author_facet Gabriela Tapia-Calle
Maaike Stoel
Jacqueline de Vries-Idema
Anke Huckriede
author_sort Gabriela Tapia-Calle
collection DOAJ
description Vaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans.
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spelling doaj.art-c4251be1c3b446f7925a65c893d2e6bb2022-12-22T04:23:26ZengMDPI AGVaccines2076-393X2017-08-01532110.3390/vaccines5030021vaccines5030021Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine FormulationsGabriela Tapia-Calle0Maaike Stoel1Jacqueline de Vries-Idema2Anke Huckriede3Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9713AV Groningen, The NetherlandsDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9713AV Groningen, The NetherlandsDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9713AV Groningen, The NetherlandsDepartment of Medical Microbiology, University of Groningen, University Medical Center Groningen, 9713AV Groningen, The NetherlandsVaccine development relies on testing vaccine candidates in animal models. However, results from animals cannot always be translated to humans. Alternative ways to screen vaccine candidates before clinical trials are therefore desirable. Dendritic cells (DCs) are the main orchestrators of the immune system and the link between innate and adaptive responses. Their activation by vaccines is an essential step in vaccine-induced immune responses. We have systematically evaluated the suitability of two different human DC-based systems, namely the DC-cell line MUTZ-3 and primary monocyte-derived DCs (Mo-DCs) to screen immunopotentiating properties of vaccine candidates. Two different influenza vaccine formulations, whole inactivated virus (WIV) and subunit (SU), were used as model antigens as they represent a high immunogenic and low immunogenic vaccine, respectively. MUTZ-3 cells were restricted in their ability to respond to different stimuli. In contrast, Mo-DCs readily responded to WIV and SU in a vaccine-specific way. WIV stimulation elicited a more vigorous induction of activation markers, immune response-related genes and secretion of cytokines involved in antiviral responses than the SU vaccine. Furthermore, Mo-DCs differentiated from freshly isolated and freeze/thawed peripheral blood mononuclear cells (PBMCs) showed a similar capacity to respond to different vaccines. Taken together, we identified human PBMC-derived Mo-DCs as a suitable platform to evaluate vaccine-induced immune responses. Importantly, we show that fresh and frozen PBMCs can be used indistinctly, which strongly facilitates the routine use of this system. In vitro vaccine pre-screening using human Mo-DCs is thus a promising approach for evaluating the immunopotentiating capacities of new vaccine formulations that have not yet been tested in humans.https://www.mdpi.com/2076-393X/5/3/21dendritic cellMUTZ-3whole inactivated virus influenza vaccinesubunit influenza vaccineflow cytometryqPCRcytokines
spellingShingle Gabriela Tapia-Calle
Maaike Stoel
Jacqueline de Vries-Idema
Anke Huckriede
Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
Vaccines
dendritic cell
MUTZ-3
whole inactivated virus influenza vaccine
subunit influenza vaccine
flow cytometry
qPCR
cytokines
title Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
title_full Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
title_fullStr Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
title_full_unstemmed Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
title_short Distinctive Responses in an In Vitro Human Dendritic Cell-Based System upon Stimulation with Different Influenza Vaccine Formulations
title_sort distinctive responses in an in vitro human dendritic cell based system upon stimulation with different influenza vaccine formulations
topic dendritic cell
MUTZ-3
whole inactivated virus influenza vaccine
subunit influenza vaccine
flow cytometry
qPCR
cytokines
url https://www.mdpi.com/2076-393X/5/3/21
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