A5006315819- Bacterial Infections and Vaccines
- Pneumonia and Respiratory Infections
- Influenza Virus Research Studies
- Monoclonal and Polyclonal Antibodies Research
- Complement system in diseases
- Virology and Viral Diseases
- Peptidase Inhibition and Analysis
- Respiratory viral infections research
- Immune Response and Inflammation
- Infective Endocarditis Diagnosis and Management
- SARS-CoV-2 and COVID-19 Research
- Neonatal and Maternal Infections
- Pharmaceutical studies and practices
- Pediatric health and respiratory diseases
- Blood groups and transfusion
- Viral gastroenteritis research and epidemiology
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- Glycosylation and Glycoproteins Research
- Amoebic Infections and Treatments
- Vaccine Coverage and Hesitancy
- Tracheal and airway disorders
- Inhalation and Respiratory Drug Delivery
- RNA and protein synthesis mechanisms
- Escherichia coli research studies
UCSF Benioff Children's Hospital
2015-2021
University of California, San Francisco
2018-2020
Pennsylvania Department of Health
2018
Children's Hospital of Pittsburgh
2018
Centers for Disease Control and Prevention
1984-2018
University of Massachusetts Chan Medical School
2008-2017
Institut de Recherche Vaccinale
2013
Oakland University
2012
Saint Louis University
1998-2004
National Institute of Allergy and Infectious Diseases
2004
Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine prevents these diseases. In this work, five antigens discovered reverse vaccinology were expressed in a form suitable for large-scale manufacturing formulated with adjuvants human use. The adjuvanted aluminum hydroxide induced bactericidal antibodies mice against 78% of panel 85 meningococcal strains representative the global...
Sepsis and meningitis caused by serogroup B meningococcus are devastating diseases of infants young adults, which cannot yet be prevented vaccination. By genome mining, we discovered GNA1870, a new surface-exposed lipoprotein Neisseria meningitidis that induces high levels bactericidal antibodies. The antigen is expressed all strains N. tested. Sequencing the gene in 71 representative genetic geographic diversity population, showed protein can divided into three variants. Conservation within...
Abstract Neisseria meningitidis binds factor H (fH), a key regulator of the alternative complement pathway. A ∼29 kD fH-binding protein expressed in meningococcal outer membrane was identified by mass spectrometry as GNA1870, lipoprotein currently under evaluation broad-spectrum vaccine candidate. GNA1870 confirmed fH ligand on intact bacteria 1) abrogation binding upon deleting and 2) blocking anti-GNA1870 mAbs. bound to whole purified rGNA1870 representing each three variant families. We...
Journal Article Subtyping Isolates of Haemophilus influenzae Type b by Outer-Membrane Protein Profiles Get access Stephen J. Barenkamp, Barenkamp Edward Mallinckrodt Department Pediatrics, Washington University School Medicine, St. Louis, MissouriDivision Infectious Diseases, Louis Children's Hospital, Missouri Please address requests for reprints to Dr. Division 500 South Kingshighway Boulevard, 63178. Search other works this author on: Oxford Academic PubMed Google Scholar Robert S....
Neisseria meningitidis is a human pathogen, which, in spite of antibiotic therapy, still major cause mortality due to sepsis and meningitis. Here we describe NadA, novel surface antigen N. that present 52 out 53 strains hypervirulent lineages electrophoretic types (ET) ET37, ET5, cluster A4. The gene absent the lineage III, gonorrhoeae commensal species lactamica cinerea. guanine/cytosine content, lower than chromosome, suggests acquisition by horizontal transfer subsequent limited evolution...
Objective. To determine whether human milk and nucleotides added to infant formula at levels present in enhance development of the immune system during infancy. Methods. A 12-month, controlled, randomized blinded, multisite feeding trial was conducted on two formulas: iron-fortified, milk-based control (Control) or same fortified with (Nucleotide). The level (72 mg/L) ratio individual selected were patterned after those available milk. third group fed exclusively for 2 months then Similac...
A collection of 242 strains Haemophilus influenzae, including 65 nontypable (unencapsulated) isolates and 177 encapsulated serotype b recovered largely from children with invasive noninvasive diseases in the United States, was characterized by electrophoretic mobilities 15 metabolic enzymes presumably encoded chromosomal genes. All were polymorphic for three to seven electromorphs, 94 distinctive multilocus genotypes (electrophoretic types [ETs]) distinguished, among which mean genetic...
A collection of 2,209 isolates six polysaccharide capsule types Haemophilus influenzae, including 1,975 serotype b recovered in 30 countries was characterized for electrophoretically demonstrable allele profiles at 17 metabolic enzyme loci. Two hundred eighty distinct multilocus genotypes were distinguished, and cluster analysis revealed two primary phylogenetic divisions. The population structure encapsulated H. influenzae is clonal. Currently, most the invasive disease worldwide caused by...
Two hundred twenty-one Gambian children vaccinated previously with one, two, or three doses of a meningococcal conjugate vaccine two polysaccharide before the age 6 months were revaccinated at 18-24 either polysaccharide, conjugate, inactivated polio vaccines. Children who had received significantly (P < .001) higher anti-group C antibody levels following revaccination than did for first time. lower group response control children. Group A responses not those in Thus, immunologic memory was...
Complement factor H (fH), a molecule that downregulates complement activation, binds to Neisseria meningitidis and increases resistance serum bactericidal activity. We investigated the species specificity of fH binding effect human on downregulating rat (relevant for animal models) rabbit vaccine evaluation) activation. Binding N. was specific (low chimpanzee not detected with from lower primates). The addition decreased C3 deposition bacterial surface group C titers measured 10- 60-fold in...
Certain pathogens recruit host complement inhibitors such as factor H (fH) to evade the immune system. Microbial inhibitor-binding molecules can be promising vaccine targets by eliciting Abs that neutralize this microbial defense mechanism. One Ag, meningococcal H-binding protein (fHbp), was used in clinical trials before discovered bind fH. The potential effect of fH binding on immunogenicity had not been assessed experimental animals because fHbp binds human specifically. In study, we...
Thirty-four adults were vaccinated with 1/50 of the usual dose meningococcal polysaccharide vaccine (1 µg A, C, Y, and W135 polysaccharides, given intramuscularly). This was selected as a probe to assess B cell memory. The elicited C bactericidal antibody responses in all 18 who had been 4 years earlier an investigational A oligosaccharide-protein conjugate majority 11 subjects for first time. In contrast, 5 full licensed <1/10 those other 2 groups. Thus, previously show evidence immunologic...
Genome-derived neisserial antigen 2132 (GNA2132) is a novel vaccine candidate that was identified during the Neisseria meningitidis group B strain MC58 genome-sequencing project. To assess potential of GNA2132, we prepared antisera from mice immunized with recombinant GNA2132 (gene NZ394/98). Anti-GNA2132 antibody bound to surface live bacteria all 7 capsular or C strains tested and elicited deposition human C3b on bacterial surface. However, infant-rat complement, anti-GNA2132 had no...
The techniques of biotype determination and sodium dodecyl sulfate-polyacrylamide gel electrophoresis outer membrane protein preparations were applied to 35 epidemiologically unrelated isolates pathogenic nontypable Haemophilus influenzae. Three five obtained from the blood newborns with sepsis had concordant major older children or adults bacteremia profiles, distinct common profile neonatal strains, II. profiles remaining 5 blood, 2 isolated cerebrospinal fluid, 23 middle ear aspirates...
Antibodies to factor H (fH)-binding protein (fHBP), a meningococcal vaccine antigen, activate classical complement pathway serum bactericidal activity (SBA) and block binding of the inhibitor fH.To understand these 2 functions in protection, we investigated interactions human anti-fHBP monoclonal antibodies (MAbs) with encapsulated Neisseria meningitidis.JAR 3 (IgG3) blocks fH elicits SBA against strains naturally high fHBP expression low-expressing strain genetically engineered express...