Oral immunization with recombinant Lactococcus lactis confers protection against respiratory pneumococcal infection

2008 ◽  
Vol 54 (10) ◽  
pp. 845-853 ◽  
Author(s):  
Julio Villena ◽  
Marcela Medina ◽  
Raúl Raya ◽  
Susana Alvarez
Keyword(s):  
Lactococcus Lactis ◽  
Protective Immunity ◽  
Protein A ◽  
Pneumococcal Infection ◽  
Interferon Γ ◽  
Oral Immunization ◽  
Interleukin 4 ◽  
Cell Counts ◽  
Recombinant Lactococcus Lactis ◽  
Th1 And Th2 Responses

In the present work, we evaluated if oral immunization with the pneumococcal protective protein A (PppA), expressed in the cell wall of Lactococcus lactis (L. lactis PppA+), was able to confer protective immunity against Streptococcus pneumoniae . Mice were immunized orally with L. lactis PppA+ for 5 consecutive days. Vaccination was performed one (nonboosted group) or 2 times with a 2 week interval between each immunization (boosted group). Oral priming with L. lactis PppA+ induced the production of anti-PppA IgM, IgG, and IgA antibodies in serum and in bronchoalveolar (BAL) and intestinal (IF) lavage fluids. Boosting with L. lactis PppA+ increased the levels of mucosal and systemic immunoglobulins. Moreover, the avidity and the opsonophagocytic activity of anti-PppA antibodies were significantly improved in the boosted group. The presence of both IgG1 and IgG2a anti-PppA antibodies in serum and BAL and the production of both interferon γ and interleukin-4 by spleen cells from immunized mice indicated that L. lactis PppA+ stimulated a mixture of Th1 and Th2 responses. The ability of L. lactis PppA+ to confer cross-protective immunity was evaluated using challenge assays with serotypes 3, 6B, 14, and 23F. Lung bacterial cell counts and hemocultures showed that immunization with L. lactis PppA+ improved resistance against all the serotypes assessed, including serotype 3, which was highly virulent in our experimental animal model. To our knowledge, this is the first demonstration of protection against respiratory pneumococcal infection induced by oral administration of a recombinant lactococcal vaccine.

scholarly journals Oral immunization of a non-recombinant Lactococcus lactis surface displaying influenza hemagglutinin 1 (HA1) induces mucosal immunity in mice

PLoS ONE ◽  
2017 ◽  
Vol 12 (11) ◽  
pp. e0187718 ◽  
Author(s):  
Pui-Fong Jee ◽  
Vunjia Tiong ◽  
Meng-Hooi Shu ◽  
Jing-Jing Khoo ◽  
Won Fen Wong ◽  
...  
Keyword(s):  
Lactococcus Lactis ◽  
Mucosal Immunity ◽  
Oral Immunization ◽  
Influenza Hemagglutinin ◽  
Recombinant Lactococcus Lactis

Immunogenicity and protective efficacy of orally administered recombinant Lactococcus lactis expressing surface-bound HIV Env

Blood ◽  
2003 ◽  
Vol 102 (1) ◽  
pp. 223-228 ◽  
Author(s):  
Ke-Qin Xin ◽  
Yuka Hoshino ◽  
Yoshihiko Toda ◽  
Shizunobu Igimi ◽  
Yoshitsugu Kojima ◽  
...  
Keyword(s):  
Immune Responses ◽  
Lactococcus Lactis ◽  
Potential Role ◽  
Protective Efficacy ◽  
Oral Immunization ◽  
Vaccine Strategy ◽  
Regional Lymph Nodes ◽  
Viral Loads ◽  
Recombinant Lactococcus Lactis ◽  
Further Development

Abstract This study investigates whether genetically modified orally administered Lactococcus lactis (L lactis) could be used as an HIV vaccine. L lactis is immunogenic and extremely safe when delivered orally. We created a recombinant L lactis vector expressing the envelope protein of HIV on its cell surface. Oral immunization with this vector induced high levels of HIV-specific serum IgG and fecal IgA antibodies. Cell-mediated immune responses also were generated in both the regional lymph nodes and the spleen. Dendritic cells are readily infected by L lactis and appear to play a potential role in mediating the development of these immune responses. The protective efficacy of this vaccine strategy was demonstrated by challenging mice intraperitoneally with an HIV Env–expressing vaccinia virus. Their viral loads were 350-fold lower than those of control mice. These findings support the further development of L lactis–based HIV vaccines. (Blood. 2003; 102:223-228)

scholarly journals Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6981-6986 ◽  
Author(s):  
Mineo Watanabe ◽  
Masaaki Nagai
Keyword(s):  
Immune Response ◽  
Respiratory Infection ◽  
Murine Model ◽  
Protective Immunity ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
Bordetella Parapertussis ◽  
Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

scholarly journals Enhanced Lung Injury and Delayed Clearance of Pneumocystis carinii in Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species

2004 ◽  
Vol 72 (10) ◽  
pp. 6002-6011 ◽  
Author(s):  
Elena N. Atochina ◽  
James M. Beck ◽  
Angela M. Preston ◽  
Angela Haczku ◽  
Yaniv Tomer ◽  
...  
Keyword(s):  
Lung Injury ◽  
Pneumocystis Carinii ◽  
Protein A ◽  
Reactive Oxygen ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Interleukin 4 ◽  
Nitrogen Species ◽  
Cell Counts ◽  
Deficient Mice

ABSTRACT Surfactant protein A (SP-A), a member of the collectin family, selectively binds to Pneumocystis carinii and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of Pneumocystis organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A−/−) with or without selective CD4+-T-cell depletion were intratracheally inoculated with Pneumocystis organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe Pneumocystis infection than CD4-depleted WT (P. carinii pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A−/− mice also had evidence of increased organism burden. Pneumocystis infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A−/− versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A−/− mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A−/− mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A−/− group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with P. carinii exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against P. carinii in vivo.

scholarly journals Production of Functionalized Biopolyester Granules by Recombinant Lactococcus lactis

2009 ◽  
Vol 75 (14) ◽  
pp. 4668-4675 ◽  
Author(s):  
Jun Mifune ◽  
Katrin Grage ◽  
Bernd H. A. Rehm
Keyword(s):  
Lactococcus Lactis ◽  
Biomedical Applications ◽  
Affinity Purification ◽  
Expression System ◽  
Protein A ◽  
Dry Weight ◽  
Enzyme Linked Immunosorbent Assay ◽  
Flight Mass Spectrometry ◽  
Igg Binding ◽  
Recombinant Lactococcus Lactis

ABSTRACT Many bacteria are naturally capable of accumulating biopolyesters composed of 3-hydroxy fatty acids as intracellular inclusions, which serve as storage granules. Recently, these inclusions have been considered as nano-/microbeads with surface-attached proteins, which can be engineered to display various protein-based functions that are suitable for biotechnological and biomedical applications. In this study, the food-grade, generally-regarded-as-safe gram-positive organism Lactococcus lactis was engineered to recombinantly produce the biopolyester poly(3-hydroxybutyrate) and the respective intracellular inclusions. The codon-optimized polyhydroxybutyrate biosynthesis operon phaCAB from Cupriavidus necator was expressed using the nisin-controlled gene expression system. Recombinant L. lactis accumulated up to 6% (wt/wt) poly(3-hydroxybutyrate) of cellular dry weight. Poly(3-hydroxybutyrate) granules were isolated and analyzed with respect to bound proteins using biochemical methods and with respect to shape/size using transmission electron microscopy. The immunoglobulin G (IgG) binding ZZ domain of Staphylococcus aureus protein A was chosen as an exemplary functionality to be displayed at the granule surface by fusing it to the N terminus of the granule-associated poly(3-hydroxybutyrate) synthase. The presence of the fusion protein at the surface of isolated granules was confirmed by peptide fingerprinting using matrix-assisted laser desorption ionization-time of flight (mass spectrometry). The functionality of the ZZ domain-displaying granules was demonstrated by enzyme-linked immunosorbent assay and IgG affinity purification. In both assays, the ZZ beads from recombinant L. lactis performed at least equally to ZZ beads from Escherichia coli. Overall, in this study it was shown that recombinant L. lactis can be used to manufacture endotoxin-free poly(3-hydroxybutyrate) beads with surface functionalities that are suitable for biomedical applications.

scholarly journals Cross-Protective Immunity of Mice Induced by Oral Immunization with Pneumococcal Surface Adhesin A Encapsulated in Microspheres

2002 ◽  
Vol 70 (3) ◽  
pp. 1143-1149 ◽  
Author(s):  
Jun-Young Seo ◽  
Seung Yong Seong ◽  
Byung-Yoon Ahn ◽  
Ick Chan Kwon ◽  
Hesson Chung ◽  
...  
Keyword(s):  
Immune System ◽  
Oral Delivery ◽  
Protective Immunity ◽  
Capsular Polysaccharide ◽  
Oral Vaccine ◽  
Pneumococcal Infection ◽  
The Elderly ◽  
Oral Immunization ◽  
Mucosal Antibody ◽  
Lung Colonization

ABSTRACT The global use of a capsular polysaccharide-based pneumococcal vaccine has been limited because of serotype-specific protection and poor effectiveness in individuals with low immunocompetency. The mucosal immune system develops earlier in infants and lasts longer in the elderly than does the systemic immune system. Furthermore, mucosal immunization is beneficial for AIDS patients, because human immunodeficiency virus-infected subjects can develop normal mucosal antibody responses even in late clinical phases. For these reasons, we evaluated recombinant pneumococcal surface adhesin A (rPsaA) of Streptococcus pneumoniae in terms of cross-protective immune responses after oral delivery. Encapsulated rPsaA provided higher immunogenicity than naked rPsaA. Coencapsulation or codelivery of the cholera toxin (CT) B subunit (CTB) and CT also increased the immunogenicity of rPsaA. Cross-protective immunities against five strains of S. pneumoniae (types 4, 6B, 14, 19F, and 23F) were induced after oral immunization with microencapsulated rPsaA. Lung colonization and septicemia caused by the five serotypes were significantly inhibited by oral immunization with microencapsulated rPsaA. These results suggest that rPsaA coencapsulated with CTB can be used as an oral vaccine to induce cross-protective immunity for the prevention of pneumococcal infection.

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