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Groningen, Netherlands

The invention relates to the field of biology, more specifically to the field of immunology and microbiology. The invention further relates to the field of vaccines against microbial infections and especially bacterial vaccines, in particular to pneumococcal vaccines. More in particular, the invention relates to means and methods to identify, select and isolate a vaccine component for passive and/or active immunisation against a microorganism that can be killed by opsonophagocytic cells. The invention relates to a method to identify an opsonophagocytosis inducing antigen as a vaccine component for immunisation against a microorganism. The invention describes three pneumococcal proteins SlrA, IgA1 proteinase, and PsaA, and their use as a vaccine component with or without PpmA. The invention also discloses the use of antibodies against said proteins for passive immunization and diagnosis.

The invention relates to the field of immunology and vaccine development, in particular to the development of vaccines based on native antigen oligomers. Provided is an immunogenic composition in particulate form, comprising oligomers of a surface exposed polypeptide of pathogenic origin or tumour origin, or antigenic part thereof, said oligomers being bound non-covalently to a particulate carrier, and a pharmaceutically acceptable diluent or excipient. Also provided is a recombinant polypeptide comprising (A) an N- or C-terminal antigenic domain, comprising at least one surface exposed polypeptide of pathogenic or tumour origin, or antigenic part thereof, the antigenic domain being fused to (B) an oligomerization domain (OMD), said oligomerization domain being fused via (C) a linker domain to (D) a peptidoglycan binding domain (PBD) consisting of a single copy of a LysM domain capable of mediating the non-covalent attachment of the polypeptide to a non-viable bacterium-like particle (BLP) obtained from a Gram-positive bacterium.

Nganou-Makamdop K.,Radboud University Nijmegen | Van Roosmalen M.L.,Mucosis BV | Audouy S.A.,BiOMaDe Technology Foundation | Van Gemert G.-J.,Radboud University Nijmegen | And 3 more authors.
Malaria Journal | Year: 2012

Background: Virus-like particles have been regularly used as an antigen delivery system for a number of Plasmodium peptides or proteins. The present study reports the immunogenicity and protective efficacy of bacterium-like particles (BLPs) generated from Lactococcus lactis and loaded with Plasmodium berghei circumsporozoite protein (PbCSP) peptides. Methods. A panel of BLP-PbCSP formulations differing in composition and quantity of B-cell, CD4+ and CD8+ T-cell epitopes of PbCSP were tested in BALB/c mice. Results: BLP-PbCSP1 induced specific humoral responses but no IFN- ELISPOT response, protecting 30-40% of the immunized mice. BLP-PbCSP2, with reduced length of the non-immunogenic part of the T-cell-epitopes construct, increased induction of IFN- responses as well as protection up to 60-70%. Compared to controls, lower parasitaemia was observed in unprotected mice immunized with BLP-PbCSP1 or 2, suggestive for partial immunity. Finally, further increase of the number of B-cell epitopes and codon optimization (BLP-PbCSP4) induced the highest anti-CSP antibody levels and number of IFN- spots, resulting in sterile immunity in 100% of the immunized mice. Conclusion: Presentation of Plasmodium-derived antigens using BLPs as a delivery system induced complete protection in a murine malaria model. Eventually, BLPs have the potential to be used as a novel versatile delivery platform in malaria vaccine development. © 2012 Nganou-Makamdop et al; licensee BioMed Central Ltd.

Ramirez K.,University of Maryland, Baltimore | Ditamo Y.,University of Maryland, Baltimore | Rodriguez L.,University of Maryland, Baltimore | Picking W.L.,Oklahoma State University | And 3 more authors.
Mucosal Immunology | Year: 2010

Safe and effective immunization of newborns and infants can significantly reduce childhood mortality, yet conventional vaccines have been largely unsuccessful in stimulating the neonatal immune system. We explored the capacity of a novel mucosal antigen delivery system consisting of non-living, non-genetically modified Lactococcus lactis particles, designated as Gram-positive enhancer matrix (GEM), to induce immune responses in the neonatal setting. Yersinia pestis LcrV, used as model protective antigen, was displayed on the GEM particles. Newborn mice immunized intranasally with GEM-LcrV developed LcrV-specific antibodies, Th1-type cell-mediated immunity, and were protected against lethal Y. pestis (plague) infection. The GEM particles activated and enhanced the maturation of neonatal dendritic cells (DCs) both in vivo and in vitro. These DCs showed increased capacities for secretion of proinflammatory and Th1-cell polarizing cytokines, antigen presentation and stimulation of CD4 and CD8 T cells. These data show that mucosal immunization with L. lactis GEM particles carrying vaccine antigens represents a promising approach to prevent infectious diseases early in life. © 2010 Society for Mucosal Immunology.

Petrovic D.M.,University of Groningen | Leenhouts K.,Mucosis BV | Van Roosmalen M.L.,Mucosis BV | Kleinjan F.,University of Groningen | Broos J.,University of Groningen
Analytical Biochemistry | Year: 2012

The lysin motif (LysM) is a peptidoglycan binding protein domain found in a wide range of prokaryotes and eukaryotes. Various techniques have been used to study the LysM-ligand interaction, but a sensitive spectroscopic method to directly monitor this interaction has not been reported. Here a tryptophan analog fluorescence spectroscopy approach is presented to monitor the LysM-ligand interaction using the LysM of the N-acetylglucosaminidase enzyme of Lactococcus lactis. A three-dimensional model of this LysM protein was built based on available structural information of a homolog. This model allowed choosing the amino acid positions to be labeled with a Trp analog. Four functional single-Trp LysM mutants and one double-Trp LysM mutant were constructed and biosynthetically labeled with 7-azatryptophan or 5-hydroxytryptophan. These Trp analogs feature red-shifted absorption spectra, enabling the monitoring of the LysM-ligand interaction in media with a Trp background. The emission intensities of four of the five LysM constructs were found to change markedly on exposure to either L. lactis bacterium-like particles or peptidoglycan as ligands. The method reported here is suitable to monitor LysM-ligand interactions at (sub)micromolar LysM concentrations and can be used for the detection of low levels of peptidoglycan or microbes in solutions. © 2012 Elsevier Inc. All rights reserved.

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