Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype

Lactococcus lactis is a promising candidate for the development of mucosal vaccines. More than 20 years of experimental research supports this immunization approach. In addition, 30 5 0 - cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that plays a key role in the r...

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Autores principales: Quintana, Ingrid M., Espariz, Martín, Villar, Silvina Raquel, González, Florencia Belén, Pacini, María F., Cabrera, Gabriel, Bontempi, Iván, Prochetto, Estefanía, Stülke, Jörg, Perez, Ana R., Marcipar, Iván, Blancato, Victor, Magni, Christian
Formato: publishedVersion
Lenguaje:Inglés
Publicado: Frontiers Media 2021
Materias:
Lactococcus lactis
C-di-AMP Adjuvant
Live Vaccines
Drug Delivery Systems
Trypanosoma cruzi
Trans-sialidase
Acceso en línea:http://hdl.handle.net/2133/20104
http://hdl.handle.net/2133/20104
Aporte de:
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) de Universidad Nacional de Rosario
id I15-R121-2133-20104
record_format dspace
institution Universidad Nacional de Rosario
institution_str I-15
repository_str R-121
collection Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR)
language Inglés
orig_language_str_mv eng
topic Lactococcus lactis
C-di-AMP Adjuvant
Live Vaccines
Drug Delivery Systems
Trypanosoma cruzi
Trans-sialidase
spellingShingle Lactococcus lactis
C-di-AMP Adjuvant
Live Vaccines
Drug Delivery Systems
Trypanosoma cruzi
Trans-sialidase
Quintana, Ingrid M.
Espariz, Martín
Villar, Silvina Raquel
González, Florencia Belén
Pacini, María F.
Cabrera, Gabriel
Bontempi, Iván
Prochetto, Estefanía
Stülke, Jörg
Perez, Ana R.
Marcipar, Iván
Blancato, Victor
Magni, Christian
Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
topic_facet Lactococcus lactis
C-di-AMP Adjuvant
Live Vaccines
Drug Delivery Systems
Trypanosoma cruzi
Trans-sialidase
description Lactococcus lactis is a promising candidate for the development of mucosal vaccines. More than 20 years of experimental research supports this immunization approach. In addition, 30 5 0 - cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that plays a key role in the regulation of diverse physiological functions (potassium and cellular wall homeostasis, among others). Moreover, recent studies showed that c-di-AMP has a strong mucosal adjuvant activity that promotes both humoral and cellular immune responses. In this study, we report the development of a novel mucosal vaccine prototype based on a genetically engineered L. lactis strain. First, we demonstrate that homologous expression of cdaA gen in L. lactis is able to increase c-di-AMP levels. Thus, we hypothesized that in vivo synthesis of the adjuvant can be combined with production of an antigen of interest in a separate form or jointly in the same strain. Therefore, a specifically designed fragment of the trans-sialidase (TScf) enzyme from the Trypanosoma cruzi parasite, the etiological agent of Chagas disease, was selected to evaluate as proof of concept the immune response triggered by our vaccine prototypes. Consequently, we found that oral administration of a L. lactis strain expressing antigenic TScf combined with another L. lactis strain producing the adjuvant c-di-AMP could elicit a TS-specific immune response. Also, an additional L. lactis strain containing a single plasmid with both cdaA and tscf genes under the Pcit and Pnis promoters, respectively, was also able to elicit a specific immune response. Thus, the current report is the first one to describe an engineered L. lactis strain that simultaneously synthesizes the adjuvant c-di-AMP as well as a heterologous antigen in order to develop a simple and economical system for the formulation of vaccine prototypes using a food grade lactic acid bacterium.
format publishedVersion
author Quintana, Ingrid M.
Espariz, Martín
Villar, Silvina Raquel
González, Florencia Belén
Pacini, María F.
Cabrera, Gabriel
Bontempi, Iván
Prochetto, Estefanía
Stülke, Jörg
Perez, Ana R.
Marcipar, Iván
Blancato, Victor
Magni, Christian
author_facet Quintana, Ingrid M.
Espariz, Martín
Villar, Silvina Raquel
González, Florencia Belén
Pacini, María F.
Cabrera, Gabriel
Bontempi, Iván
Prochetto, Estefanía
Stülke, Jörg
Perez, Ana R.
Marcipar, Iván
Blancato, Victor
Magni, Christian
author_sort Quintana, Ingrid M.
title Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
title_short Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
title_full Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
title_fullStr Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
title_full_unstemmed Genetic engineering of Lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-AMP) as a design strategy to develop a mucosal vaccine prototype
title_sort genetic engineering of lactococcus lactis co-producing antigen and the mucosal adjuvant 3′ 5′- cyclic di adenosine monophosphate (c-di-amp) as a design strategy to develop a mucosal vaccine prototype
publisher Frontiers Media
publishDate 2021
url http://hdl.handle.net/2133/20104
http://hdl.handle.net/2133/20104
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