Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model

Group B <i>Streptococcus</i> (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed...

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Main Authors: Diego A. Diaz-Dinamarca, Carlos Hernandez, Daniel F. Escobar, Daniel A. Soto, Guillermo A. Muñoz, Jesús F. Badilla, Ricardo A. Manzo, Flavio Carrión, Alexis M. Kalergis, Abel E. Vasquez
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/8/2/146
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spelling doaj-3dc01393e7eb4aa5ae875c673e13228c2020-11-25T03:10:06ZengMDPI AGVaccines2076-393X2020-03-018214610.3390/vaccines8020146vaccines8020146Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine ModelDiego A. Diaz-Dinamarca0Carlos Hernandez1Daniel F. Escobar2Daniel A. Soto3Guillermo A. Muñoz4Jesús F. Badilla5Ricardo A. Manzo6Flavio Carrión7Alexis M. Kalergis8Abel E. Vasquez9Sección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChilePrograma de Inmunología Traslacional, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 7610315, ChileMillennium Institute of Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8380453, ChileSección de Biotecnología, Instituto de Salud Pública de Chile, Santiago 780050, ChileGroup B <i>Streptococcus</i> (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. <i>Lactococcus lactis</i> is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant <i>L. lactis</i> strain secreting SIP from GBS (<i>rL. lactis</i>-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with <i>rL. lactis-</i>SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our <i>rL. lactis-</i>SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to na&#239;ve mice generated protection against GBS vaginal colonization. Moreover, the <i>rL.</i> <i>lactis</i>-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that <i>rL. lactis</i>-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.https://www.mdpi.com/2076-393X/8/2/146group b streptococcusmucosal vaccinesurface immunogenic proteincellular immune responsehumoral immune response
collection DOAJ
language English
format Article
sources DOAJ
author Diego A. Diaz-Dinamarca
Carlos Hernandez
Daniel F. Escobar
Daniel A. Soto
Guillermo A. Muñoz
Jesús F. Badilla
Ricardo A. Manzo
Flavio Carrión
Alexis M. Kalergis
Abel E. Vasquez
spellingShingle Diego A. Diaz-Dinamarca
Carlos Hernandez
Daniel F. Escobar
Daniel A. Soto
Guillermo A. Muñoz
Jesús F. Badilla
Ricardo A. Manzo
Flavio Carrión
Alexis M. Kalergis
Abel E. Vasquez
Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
Vaccines
group b streptococcus
mucosal vaccine
surface immunogenic protein
cellular immune response
humoral immune response
author_facet Diego A. Diaz-Dinamarca
Carlos Hernandez
Daniel F. Escobar
Daniel A. Soto
Guillermo A. Muñoz
Jesús F. Badilla
Ricardo A. Manzo
Flavio Carrión
Alexis M. Kalergis
Abel E. Vasquez
author_sort Diego A. Diaz-Dinamarca
title Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
title_short Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
title_full Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
title_fullStr Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
title_full_unstemmed Mucosal Vaccination with <i>Lactococcus lactis</i>-Secreting Surface Immunological Protein Induces Humoral and Cellular Immune Protection against Group B <i>Streptococcus</i> in a Murine Model
title_sort mucosal vaccination with <i>lactococcus lactis</i>-secreting surface immunological protein induces humoral and cellular immune protection against group b <i>streptococcus</i> in a murine model
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2020-03-01
description Group B <i>Streptococcus</i> (GBS) is the primary etiological agent of sepsis and meningitis in newborns and is associated with premature birth and stillbirth. The development of a licensed vaccine is one of the pending challenges for the World Health Organization. Previously, we showed that oral immunization with surface immune protein (SIP) decreases vaginal colonization of GBS and generates functional opsonizing antibodies, which was determined by opsonophagocytic assays (OPA) in vitro. We also showed that the protein has an adjuvant vaccine profile. Therefore, an oral vaccine based on SIP may be an attractive alternative to employ in the development of new vaccines against GBS. <i>Lactococcus lactis</i> is a highlighted oral vaccine probiotic inducer of the mucosal immune response. This bacterium could serve as an antigen-delivering vehicle for the development of an edible vaccine and has been used in clinical trials. In this study, we showed that an oral vaccine with a recombinant <i>L. lactis</i> strain secreting SIP from GBS (<i>rL. lactis</i>-SIP) can induce protective humoral and cellular immunity in an experimental model of GBS vaginal colonization in C57BL/6 mice. Mice immunized with <i>rL. lactis-</i>SIP were protected against clinical symptoms and bacterial colonization after GBS vaginal colonization. Our <i>rL. lactis-</i>SIP vaccine also induces an increase of immunoglobulin G (IgG) and immunoglobulin A (IgA) specifically against SIP. The adoptive transfer of serum from vaccinated mice to na&#239;ve mice generated protection against GBS vaginal colonization. Moreover, the <i>rL.</i> <i>lactis</i>-SIP strain induces the activation of SIP-specific T cells, which could decrease GBS vaginal colonization and generate protective antibodies when transferred to other mice. Our experimental observations strongly support the notion that <i>rL. lactis</i>-SIP induces protective humoral and cellular immunity and could be considered as a novel alternative in the development of vaccines for GBS.
topic group b streptococcus
mucosal vaccine
surface immunogenic protein
cellular immune response
humoral immune response
url https://www.mdpi.com/2076-393X/8/2/146
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