Abstract:
:Binding of the complement-downregulating protein factor H (fH) to the surface of the meningococcus is important for survival of the organism in human serum. The meningococcal vaccine candidate factor H binding protein (fHbp) is an important ligand for human fH. While some fHbp-specific monoclonal antibodies (MAbs) block binding of fH to fHbp, the stoichiometry of blocking in the presence of high serum concentrations of fH and its effect on complement-mediated bactericidal activity are unknown. To investigate this question, we constructed chimeric antibodies in which the human IgG1 constant region was paired with three murine fHbp-specific binding domains designated JAR 3, JAR 5, and MAb502. By surface plasmon resonance, the association rates for binding of all three MAbs to immobilized fHbp were >50-fold higher than that for binding of fH to fHbp, and the MAb dissociation rates were >500-fold lower than that for fH. While all three MAbs elicited similar C1q-dependent C4b deposition on live bacteria (classical complement pathway), only those antibodies that inhibited binding of fH to fHbp (JAR 3 and JAR 5) had bactericidal activity with human complement. MAb502, which did not inhibit fH binding, had complement-mediated bactericidal activity only when tested with fH-depleted human complement. When an IgG1 anti-fHbp MAb binds to sparsely exposed fHbp on the bacterial surface, there appears to be insufficient complement activation for bacteriolysis unless fH binding also is inhibited. The ability of fHbp vaccines to elicit protective antibodies, therefore, is likely to be enhanced if the antibody repertoire is of high avidity and includes fH-blocking activity.
journal_name
Infect Immunjournal_title
Infection and immunityauthors
Giuntini S,Reason DC,Granoff DMdoi
10.1128/IAI.05182-11subject
Has Abstractpub_date
2011-09-01 00:00:00pages
3751-9issue
9eissn
0019-9567issn
1098-5522pii
IAI.05182-11journal_volume
79pub_type
杂志文章abstract::Previous studies showed that Pseudomonas aeruginosa exotoxin A (PA toxin) catalyzes nicotinamide adenine dinucleotide (NAD)-dependent inhibition of protein synthesis in a rabbit reticulocyte lysate and transfer of radioactivity from [14C]adenine-labeled NAD to a protein having the same molecular weight as elongation f...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.15.1.138-144.1977
更新日期:1977-01-01 00:00:00
abstract::Rhodococcus equi is a facultative intracellular pathogen of macrophages, relying on the presence of a conjugative virulence plasmid harboring a 21-kb pathogenicity island (PAI) for growth in host macrophages. The PAI encodes a family of 6 virulence-associated proteins (Vaps) in addition to 20 other proteins. The contr...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00230-15
更新日期:2015-08-01 00:00:00
abstract::Immunologically competent mice and mice with defined immunological deficiencies were infected with Plasmodium yoelii. Splenomegaly, enhanced phagocytosis, and anemia were most marked in infected mice having intact thymic tissue. Whereas the spleens of infected nude mice increased minimally in size, the relative blood ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.20.3.728-731.1978
更新日期:1978-06-01 00:00:00
abstract::Group A streptococci (GAS) are highly prevalent human pathogens whose primary ecological niche is the superficial epithelial layers of the throat and/or skin. Many GAS strains with a strong tendency to cause pharyngitis are distinct from strains that tend to cause impetigo; thus, genetic differences between them may c...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00374-17
更新日期:2017-10-18 00:00:00
abstract::Liver-stage antigen 1 (LSA-1) is a potential vaccine candidate against preerythrocytic stages of malaria. We report here the immunogenicity of linear synthetic constructs delineated as T(H)-cell determinants from the nonrepeat regions of Plasmodium falciparum LSA-1 in murine models and human subjects from areas where ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.68.1.141-150.2000
更新日期:2000-01-01 00:00:00
abstract::Detailed structural studies were undertaken on five isolates of bovine rotavirus which showed variability in the migration patterns of their genome segments on electrophoresis in polyacrylamide gels. The individual genome segments of each isolate were characterized by partial digestion of terminally radiolabeled RNA w...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.36.2.492-497.1982
更新日期:1982-05-01 00:00:00
abstract::Outer membrane porin genes of Salmonella typhimurium, including ompC, ompF, and tppB, are regulated by the products of ompB, a two-component regulatory locus encoding OmpR and EnvZ. S. typhimurium ompR mutants are attenuated in mice, but to date no one has studied the intracellular trafficking of S. typhimurium porin-...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.66.4.1806-1811.1998
更新日期:1998-04-01 00:00:00
abstract::Infantile gastroenteritis virus (orbi-group) recovered from stools of infants with acute nonbacterial gastroenteritis was administered per os to germfree and conventional piglets. Virus was found subsequently in stools and in the mucosal epithelial cells of the small intestine of these animals. Some animals developed ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.6.1276-1280.1975
更新日期:1975-12-01 00:00:00
abstract::Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3- to 4-week period. The organs of animals were proces...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.55.7.1558-1563.1987
更新日期:1987-07-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.73.7.4112-4118.2005
更新日期:2005-07-01 00:00:00
abstract::Toxoplasma gondii is an obligate intracellular parasite that resides in the cytoplasm of its host in a unique membrane-bound vacuole known as the parasitophorous vacuole (PV). The membrane surrounding the parasite is remodeled by the dense granules, secretory organelles that release an array of proteins into the vacuo...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00782-08
更新日期:2008-11-01 00:00:00
abstract::The Lyme disease spirochete, Borrelia burgdorferi, is introduced into human hosts via tick bites. Among the cell types present in the skin which may initially contact spirochetes are mast cells. Since spirochetes are known to activate a variety of cell types in vitro, we tested whether B. burgdorferi spirochetes could...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.3.1107-1115.1999
更新日期:1999-03-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.71.4.1763-1773.2003
更新日期:2003-04-01 00:00:00
abstract::Streptococcus pneumoniae is the most common pathogen associated with otitis media. To examine the role of Toll-like receptor 2 (TLR2) in host defense against Streptococcus pneumoniae infection in the middle ear, wild-type (WT; C57BL/6) and TLR2-deficient (TLR2(-/-)) mice were inoculated with Streptococcus pneumoniae (...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00204-09
更新日期:2009-07-01 00:00:00
abstract::Staphylococcus aureus and Salmonella enterica serovar Dublin invade osteoblasts and are causative agents of human bone disease. In the present study, we examined the ability of S. aureus and Salmonella serovar Dublin to induce the production of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) by normal ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.3.1581-1586.2001
更新日期:2001-03-01 00:00:00
abstract::Rheumatoid arthritis (RA) is an inflammatory disease that has been linked to several risk factors, including periodontitis. Identification of new anti-inflammatory compounds to treat arthritis is needed. We had previously demonstrated the beneficial effect of Kava-241, a kavain-derived compound, in the management of P...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00356-18
更新日期:2018-08-22 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.12.5.1029-1036.1975
更新日期:1975-11-01 00:00:00
abstract::Tetanus neurotoxin (TeNT) and botulinum neurotoxin (BoNT) are clostridial neurotoxins (CNTs) responsible for the paralytic diseases tetanus and botulism, respectively. CNTs are AB toxins with an N-terminal zinc-metalloprotease light chain that is linked by a disulfide bond to a C-terminal heavy chain that includes a t...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.01539-13
更新日期:2014-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.21.2.546-555.1978
更新日期:1978-08-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.15.2.444-452.1977
更新日期:1977-02-01 00:00:00
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journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/iai.70.4.2215-2219.2002
更新日期:2002-04-01 00:00:00
abstract::Chlamydia trachomatis serovar L2 is an obligate intracellular bacterium which is internalized in target epithelial cells by endocytosis and resides within a membrane-bound vesicle. Over the next several hours following entry, individual serovar L2-containing vesicles fuse with one another to form a single membrane-bou...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.64.4.1208-1214.1996
更新日期:1996-04-01 00:00:00
abstract::Cholera is an acute diarrheal disease that is caused by the gram-negative bacterium Vibrio cholerae. The low efficacy of currently available killed-whole-cell vaccines and the reactinogenicity coupled with potential reversion of live vaccines have thus far precluded widespread vaccination for the control of cholera. R...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.69.12.7695-7702.2001
更新日期:2001-12-01 00:00:00
abstract::Adherence of blastoconidia to epidermal corneocytes is an early event in Candida colonization and infection of the skin. Pathogenic species adhere more avidly than nonpathogenic species, transform to hyphal growth, and invade the stratum corneum of the skin. Adherence was studied by scanning electron microscopy of exp...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.56.8.1942-1949.1988
更新日期:1988-08-01 00:00:00
abstract::Phospholipase A2 and lysophospholipase activities were detected in the culture supernatant fluids of a virulent strain of Vibrio vulnificus. The phospholipase A2 was inactivated by heating at 56 degrees C for 30 min, had an apparent molecular weight of greater than or equal to 80,000 (estimated by gel filtration with ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.45.2.458-463.1984
更新日期:1984-08-01 00:00:00
abstract::Sendai virus hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins, F and HN, were separated from Triton X-100- or Nonidet P-40-solubilized envelopes as unadsorbed and eluted fractions, respectively, by using glutaralde-hyde-treated chicken erythrocytes. These separated glycoproteins were biologically active. ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.30.1.212-218.1980
更新日期:1980-10-01 00:00:00
abstract::Virulent Streptococcus suis serotype 2 strains are invasive extracellular bacteria causing septicemia and meningitis in piglets and humans. One objective of this study was to elucidate the function of complement in innate immune defense against S. suis. Experimental infection of wild-type (WT) and C3(-/-) mice demonst...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.00080-14
更新日期:2014-06-01 00:00:00
abstract::After uptake and retrograde transport pertussis toxin acts by ADP-ribosylating alpha-Gi proteins. We show that uptake via many different receptor proteins followed by retrograde transport and intoxication is not restricted to a particular cell type. The efficiency of cellular intoxication, however, was found to be cel...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.67.1.433-435.1999
更新日期:1999-01-01 00:00:00
abstract::A murine monoclonal antibody was raised against the B95-8 strain of Epstein-Barr virus (EBV), which was isolated from a case of mononucleosis after blood transfusion (Hoffman et al. Proc. Natl. Acad. Sci. U.S.A. 77:2979, 1980). We provide evidence that neutralization of immortalization by this monoclonal antibody is v...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.37.3.1028-1031.1982
更新日期:1982-09-01 00:00:00
abstract::The genetic determinants of the 120-kDa cytotoxin of Actinobacillus pleuropneumoniae serotype 2 were isolated from a lambda DNA library by a plaque immunoblot technique. Expression of the 120-kDa polypeptide was confirmed by Western immunoblot analysis of infected Escherichia coli cell lysates, which were shown to be ...
journal_title:Infection and immunity
pub_type: 杂志文章
doi:10.1128/IAI.60.7.2726-2732.1992
更新日期:1992-07-01 00:00:00