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
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Date
2018-09-04
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Frontiers Media
Abstract
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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.
Para citar este articulo: Quintana I, Espariz M, Villar SR, González FB, Pacini MF, Cabrera G, Bontempi I, Prochetto E, Stülke J, Perez AR, Marcipar I, Blancato V and Magni C (2018) Genetic Engineering of Lactococcus lactis Co-producing Antigen and the Mucosal Adjuvant 30 5 0 - cyclic di Adenosine Monophosphate (c-di-AMP) as a Design Strategy to Develop a Mucosal Vaccine Prototype. Front. Microbiol. 9:2100. doi: 10.3389/fmicb.2018.02100
Para citar este articulo: Quintana I, Espariz M, Villar SR, González FB, Pacini MF, Cabrera G, Bontempi I, Prochetto E, Stülke J, Perez AR, Marcipar I, Blancato V and Magni C (2018) Genetic Engineering of Lactococcus lactis Co-producing Antigen and the Mucosal Adjuvant 30 5 0 - cyclic di Adenosine Monophosphate (c-di-AMP) as a Design Strategy to Develop a Mucosal Vaccine Prototype. Front. Microbiol. 9:2100. doi: 10.3389/fmicb.2018.02100
Keywords
Lactococcus lactis, C-di-AMP Adjuvant, Live Vaccines, Drug Delivery Systems, Trypanosoma cruzi, Trans-sialidase