scholarly journals Immunization with SP_1992 (DiiA) Protein of Streptococcus pneumoniae Reduces Nasopharyngeal Colonization and Protects against Invasive Disease in Mice

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 187
Author(s):  
Antonio J. Martín-Galiano ◽  
María S. Escolano-Martínez ◽  
Bruno Corsini ◽  
Adela G. de la Campa ◽  
José Yuste
Keyword(s):  
Bacterial Colonization ◽  
Survival Rates ◽  
Surface Protein ◽  
Invasive Disease ◽  
Carrier State ◽  
Nasopharyngeal Colonization ◽  
Knowledge Based ◽  
Core Proteome ◽  
New Generation ◽  
Immunogenic Response

Knowledge-based vaccinology can reveal uncharacterized antigen candidates for a new generation of protein-based anti-pneumococcal vaccines. DiiA, encoded by the sp_1992 locus, is a surface protein containing either one or two repeats of a 37mer N-terminal motif that exhibits low interstrain variability. DiiA belongs to the core proteome, contains several conserved B-cell epitopes, and is associated with colonization and pathogenesis. Immunization with DiiA protein via the intraperitoneal route induced a strong IgG response, including different IgG subtypes. Vaccination with DiiA increased bacterial clearance and induced protection against sepsis, conferring 70% increased survival at 48 h post-infection when compared to the adjuvant control. The immunogenic response and survival rates in mice immunized with a truncated DiiA version lacking 119 N-terminal residues were remarkably lower, confirming the relevance of the repeat zone in the immunoprotection by DiiA. Intranasal immunization of mice with the entire recombinant protein elicited mucosal IgG and IgA responses that reduced bacterial colonization of the nasopharynx, confirming that this protein might be a vaccine candidate for reducing the carrier rate. DiiA constitutes an example of how functionally unannotated proteins may still represent promising candidates that can be used in prophylactic strategies against the pneumococcal carrier state and invasive disease.

scholarly journals Intranasal Vaccination with Pneumococcal Surface Protein A and Interleukin-12 Augments Antibody-Mediated Opsonization and Protective Immunity against Streptococcus pneumoniae Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6718-6724 ◽  
Author(s):  
Bernard P. Arulanandam ◽  
Joyce M. Lynch ◽  
David E. Briles ◽  
Susan Hollingshead ◽  
Dennis W. Metzger
Keyword(s):  
Streptococcus Pneumoniae ◽  
Bacterial Colonization ◽  
Protein A ◽  
Flow Cytometric Analysis ◽  
Surface Protein ◽  
Invasive Disease ◽  
Interleukin 12 ◽  
Opsonic Activity ◽  
Pneumococcal Surface Protein A ◽  
Optimal Approach

ABSTRACT Streptococcus pneumoniae is a major pathogen in humans that enters the host primarily through the respiratory tract. Targeting mucosal surfaces directly may therefore be an optimal approach for vaccination to prevent bacterial colonization and invasive disease. We have previously demonstrated the effectiveness of interleukin-12 (IL-12) delivered intransally (i.n.) as an antiviral respiratory adjuvant. In this study, we examined the effects of i.n. IL-12 treatment on induction of protective humoral immunity against S. pneumoniae. Immunization i.n. with pneumococcal surface protein A (PspA) and IL-12 resulted in enhanced lung IL-10 mRNA expression and marked augmentation of respiratory and systemic immunoglobulin G1 (IgG1), IgG2a, and IgA antibody levels compared to those in animals receiving PspA alone. In addition, i.n. vaccination with PspA and IL-12 provided increased protection against nasopharyngeal carriage. Flow cytometric analysis revealed a threefold increase in antibody-mediated, complement-independent opsonic activity in the sera of PspA- and IL-12-treated animals, which was mainly contributed by IgG2a and, to a lesser extent, IgA. Passive transfer of these immune sera conferred complete protection from death upon systemic pneumococcal challenge. These findings demonstrate the effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal antibody-mediated opsonization and killing of S. pneumoniae.

scholarly journals NontypeableHaemophilus influenzaeInvasive Blood Isolates Are Mainly Phosphorylcholine Negative and Show Decreased Complement-Mediated Killing That Is Associated with Lower Binding of IgM and CRP in Comparison to Colonizing Isolates from the Oropharynx

2018 ◽  
Vol 87 (2) ◽  
Author(s):  
Jeroen D. Langereis ◽  
Amelieke J. H. Cremers ◽  
Marloes Vissers ◽  
Josine van Beek ◽  
Jacques F. Meis ◽  
...  
Keyword(s):  
Human Serum ◽  
Invasive Disease ◽  
Complement C3 ◽  
Classical Pathway ◽  
Nasopharyngeal Colonization ◽  
Content Type ◽  
Specific Antibodies ◽  
Bacterial Surface ◽  
Reactive Protein ◽  
Serum Killing

ABSTRACTNontypeableHaemophilus influenzae(NTHi) bacteria express various molecules that contribute to their virulence. The presence of phosphocholine (PCho) on NTHi lipooligosaccharide increases adhesion to epithelial cells and is an advantage for the bacterium, enabling nasopharyngeal colonization, as measured in humans and animal models. However, when PCho is expressed on the lipooligosaccharide, it is also recognized by the acute-phase protein C-reactive protein (CRP) and PCho-specific antibodies, both of which are potent initiators of the classical pathway of complement activation. In this study, we show that blood isolates, which are exposed to CRP and PCho-specific antibodies in the bloodstream, have a higher survival in serum than oropharyngeal isolates, which was associated with a decreased presence of PCho. PCholowstrains showed decreased IgM, CRP, and complement C3 deposition, which was associated with increased survival in human serum. Consistent with the case for the PCholowstrains, removal of PCho expression bylicAgene deletion decreased IgM, CRP, and complement C3 deposition, which increased survival in human serum. Complement-mediated killing of PChohighstrains was mainly dependent on binding of IgM to the bacterial surface. These data support the hypothesis that a PCholowphenotype was selected in blood during invasive disease, which increased resistance to serum killing, mainly due to lowered IgM and CRP binding to the bacterial surface.

Association between maternal Group B Streptococcus surface-protein antibody concentrations and invasive disease in their infants

2015 ◽  
Vol 14 (12) ◽  
pp. 1651-1660 ◽  
Author(s):  
Ziyaad Dangor ◽  
Gaurav Kwatra ◽  
Alane Izu ◽  
Peter Adrian ◽  
Clare L Cutland ◽  
...  
Keyword(s):  
Group B Streptococcus ◽  
Surface Protein ◽  
Invasive Disease ◽  
Group B

scholarly journals Contributions of Pneumolysin, Pneumococcal Surface Protein A (PspA), and PspC to Pathogenicity of Streptococcus pneumoniae D39 in a Mouse Model

2007 ◽  
Vol 75 (4) ◽  
pp. 1843-1851 ◽  
Author(s):  
Abiodun D. Ogunniyi ◽  
Kim S. LeMessurier ◽  
Rikki M. A. Graham ◽  
James M. Watt ◽  
David E. Briles ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Systemic Disease ◽  
Protein A ◽  
Virulence Gene ◽  
Surface Protein ◽  
Invasive Disease ◽  
Upper Respiratory Tract ◽  
Virulence Proteins ◽  
Pneumococcal Surface Protein A ◽  
Genes Encoding

ABSTRACTSuccessful colonization of the upper respiratory tract byStreptococcus pneumoniaeis an essential first step in the pathogenesis of pneumococcal disease. However, the bacterial and host factors that provoke the progression from asymptomatic colonization to invasive disease are yet to be fully defined. In this study, we investigated the effects of single and combined mutations in genes encoding pneumolysin (Ply), pneumococcal surface protein A (PspA), and pneumococcal surface protein C (PspC, also known as choline-binding protein A) on the pathogenicity ofStreptococcus pneumoniaeserotype 2 (D39) in mice. Following intranasal challenge with D39, stable colonization of the nasopharynx was maintained over a 7-day period at a level of approximately 105bacteria per mouse. The abilities of the mutant deficient in PspA to colonize the nasopharynx and to cause lung infection and bacteremia were significantly reduced. Likewise, the PspC mutant and, to a lesser extent, the Ply mutant also had reduced abilities to colonize the nasopharynx. As expected, the double mutants colonized less well than the parent to various degrees and had difficulty translocating to the lungs and blood. A significant additive attenuation was observed for the double and triple mutants in pneumonia and systemic disease models. Surprisingly, the colonization profile of the derivative lacking all three proteins was similar to that of the wild type, indicating virulence gene compensation. These findings further demonstrate that the mechanism of pneumococcal pathogenesis is highly complex and multifactorial but ascribes a role for each of these virulence proteins, alone or in combination, in the process.

scholarly journals Nasopharyngeal colonization at birth and the development of early-onset neonatal sepsis

2020 ◽  
Vol 60 (6) ◽  
pp. 287-92
Author(s):  
Andi Dwi Bahagia Febriani ◽  
Nilam Sartika Putri ◽  
Ema Alasiry ◽  
Dasril Daud
Keyword(s):  
Blood Culture ◽  
Neonatal Sepsis ◽  
Early Onset ◽  
Bacterial Colonization ◽  
Bacterial Species ◽  
Nasopharyngeal Swab ◽  
Nasopharyngeal Colonization ◽  
Blood Culture Isolate ◽  
Significant Difference ◽  
Culture Isolate

Background Neonatal sepsis is one of the major causes of morbidity and mortality in neonates. Exposure to maternal bacteria during pregnancy or delivery allows for colonization of the normal upper airway. Such bacteria become the major ecological species in the infant. If the colonizing bacteria invade the bloodstream, early-onset neonatal sepsis (EONS) could occur. Objective To evaluate for an association between colonization of the newborn nasopharynx and EONS, as well as for agreement between nasopharyngeal swab culture and blood culture isolate results. Methods This prospective cohort study was conducted in Dr. Wahidin Sudirohusodo General Hospital and Ibnu Sina Hospital, Makassar, South Sulawesi. Nasopharyngeal swab culture was taken within 2 hours of life from newborns who met the inclusion criteria, then they were followed up for signs of EONS. Blood culture was taken from subject with EONS. Results Of the 100 newborns, 69 (69%) had nasopharyngeal bacterial colonization, of whom 5.8% (4/69) experienced EONS. Of the remaining 31 (31%) without colonization, 9.7% (3/31) experienced EONS. There was no significant difference in frequency of EONS between newborns with and without nasopharyngeal colonization. Although Gram-negative bacteria were predominant among colonized newborns, there was no significant difference to numbers of Gram-positive bacteria as a causative agent of EONS. Only one patient with EONS had the same bacterial species in both the nasopharynx and blood culture isolate. Conclusion  Newborn nasopharyngeal colonization at birth is not associated with EONS.

scholarly journals Differences in bacterial colonization and mucosal responses between high and low SES children in Indonesia

2021 ◽  
Author(s):  
Marloes Machilia Adriana Roosevelt van Dorst ◽  
Shohreh Azimi ◽  
Sitti Wahyuni ◽  
Aldian Irma Amarrudin ◽  
Erliyani Sartono ◽  
...  
Keyword(s):  
Immune Responses ◽  
Low Socioeconomic Status ◽  
Moraxella Catarrhalis ◽  
Pathogenic Bacteria ◽  
Bacterial Colonization ◽  
Invasive Disease ◽  
Low Ses ◽  
Nasopharyngeal Carriage ◽  
Low Socioeconomic ◽  
And Staphylococcus Aureus

BACKGROUND: Nasopharyngeal carriage of pathogenic bacteria precedes invasive disease and higher rates are found in low socioeconomic-status (SES) settings. Local immune responses are important for controlling colonization, but whether SES affects these responses is currently unknown. OBJECTIVE: Examining bacterial colonization and cytokine response in nasal mucosa of children from high and low SES. METHODS: Twenty-five cytokines were measured in nasal fluid. qPCR was performed to determine carriage and density of Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae), Moraxella catarrhalis (M. catarrhalis) and Staphylococcus aureus (S. aureus). RESULTS: The densities of H. influenzae and S. pneumoniae were increased in low compared to the high SES (p=0.006, p=0.026), with respectively 6 and 67 times higher median densities. Densities of H. influenzae and S. pneumoniae were positively associated with levels of IL-1beta (p=0.002, p=0.008) and IL-6 (p<0.001, p=0.006). After correcting for bacterial density, IL-6 levels were increased in colonized children from high compared to low SES for both H. influenzae and S. pneumoniae (both p=0.039). CONCLUSION: Increased density of H. influenzae and S. pneumoniae was observed in low SES children, while IL-6 levels associated with colonization were reduced in these children, indicating that immune responses to bacterial colonization were altered by SES.

scholarly journals Genetic Immunization with the Region Encoding the α-Helical Domain of PspA Elicits Protective Immunity againstStreptococcus pneumoniae

2001 ◽  
Vol 69 (9) ◽  
pp. 5456-5463 ◽  
Author(s):  
Joseph R. Bosarge ◽  
James M. Watt ◽  
D. Olga McDaniel ◽  
Edwin Swiatlo ◽  
Larry S. McDaniel
Keyword(s):  
Protein A ◽  
Survival Rates ◽  
Serum Antibody ◽  
Pneumococcal Infection ◽  
Surface Protein ◽  
Eukaryotic Expression ◽  
Dependent Manner ◽  
Genetic Immunization ◽  
Helical Domain ◽  
Dose Dependent

ABSTRACT Pneumococcal surface protein A (PspA) is a pneumococcal virulence factor capable of eliciting protection against pneumococcal infection in mice. Previous studies have demonstrated that the protection is antibody mediated. Here we examined the ability ofpspA to elicit a protective immune response following genetic immunization of mice. Mice were immunized by intramuscular injections with a eukaryotic expression vector encoding the α-helical domain of PspA/Rx1. Immunization induced a PspA-specific serum antibody response, and immunized mice survived pneumococcal challenge. Survival and antibody responses occurred in a dose-dependent manner, the highest survival rates being seen with doses of 10 μg or greater. The ability of genetic immunization to elicit cross-protection was demonstrated by the survival of immunized mice challenged with pneumococcal strains differing in capsule and PspA types. Also, immunized mice were protected from intravenous and intratracheal challenges with pneumococci. Similar to the results seen with immunization with PspA, the survival of mice genetically immunized with pspA was antibody mediated. There was no decline in the level of protection 7 months after immunization. These results support the use of genetic immunization to elicit protective immune responses against extracellular pathogens.

Knowledge-Based Intermediaries

2010 ◽  
pp. 191-205
Author(s):  
Levent V. Orman
Keyword(s):  
Semantic Web ◽  
Information Technologies ◽  
Electronic Markets ◽  
Rule Based ◽  
Knowledge Based ◽  
New Information ◽  
Maintenance Systems ◽  
Multiple Levels ◽  
Organizational Architecture ◽  
New Generation

A new generation of intermediaries is predicted to flourish in the emerging electronic markets. They rely on new information technologies such as the semantic web, rule-based triggers, and knowledge-based constraint maintenance systems. These technologies do not automate or reduce intermediation, but inspire new types of intermediaries that rely on the technologies and complement them with human organizations. An inter-organizational architecture based on multiple levels of intermediation is described, and arguments are presented for its usefulness in emerging electronic markets.

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