Development of flow cytometric opsonophagocytosis and antibody-mediated complement deposition assays for non-typeable Haemophilus influenzae.

Background: Haemophilus influenzae is found in the nasopharynx of 80% of the human population. While colonisation with non-typeable Haemophilus influenzae (NTHi) is usually asymptomatic, it is capable of causing acute and chronic otitis media (OM) in infants, invasive disease in susceptible groups and is the leading cause of exacerbations of patients with chronic obstructive pulmonary disease (COPD). Current methods for assessing functional antibody immunity to NTHi are limited and labour intensive.

Safety and immunogenicity of an investigational 4-component Staphylococcus aureus vaccine with or without AS03B adjuvant: Results of a randomized phase I trial.

We assessed the safety, reactogenicity and immunogenicity of a staphylococcal vaccine combining capsular polysaccharides types 5 and 8 (CPS5/8), conjugated to tetanus toxoid (TT), with mutated detoxified α-toxin (AT) and clumping factor A (ClfA). In this phase I, randomized, placebo-controlled, observer-blind trial (NCT01160172), 88 healthy 18- to 40-year-olds received CPS5-TT/CPS8-TT/AT/ClfA vaccine (5/5/10/10 μg or 10/10/30/30 μg dose, each with or without AS03B adjuvant) or saline, at months 0, 1, 6. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 d post-vaccination, respectively; potential immune-mediated diseases (pIMDs) and serious AEs (SAEs) were recorded throughout the study.

Safety, immunogenicity, and antibody persistence following an investigational Streptococcus pneumoniae and Haemophilus influenzae triple-protein vaccine in a phase 1 randomized controlled study in healthy adults.

We investigated a protein-based nontypeable Haemophilus influenzae (NTHi) and pneumococcal (HiP) vaccine containing pneumococcal histidine triad D (PhtD), detoxified pneumolysin (dPly), and NTHi protein D (PD) in adults. In a phase I study, 40 healthy 18- to 40-year-old subjects were randomized (2:2:1) to receive two HiP doses administered 60 days apart, with or without AS03 adjuvant (HiP-AS and HiP groups, respectively), or Engerix B (GlaxoSmithKline, Belgium) as a control. Safety, antibodies, and antigen-specific CD4(+) T-cell immune responses were assessed before and until 480 days after vaccination.

One or two doses of quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine is immunogenic in 9- to 12-month-old children.

Background: The incidence of invasive meningococcal disease is highest in infants. A quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) was evaluated in children 9-12 months of age.

Methods: We randomized infants (1:1) to receive 1 dose of MenACWY-TT at 12 months of age (ACWY-1 group) or 2 doses at 9 and 12 months (ACWY-2).

Immunogenicity and safety of H influenzae type b-N meningitidis C/Y conjugate vaccine in infants.

Background: Meningococcal disease incidence is highest in children younger than 2 years of age, yet there is no US-licensed vaccine for this age group. A phase III study evaluated the immunogenicity and safety of an investigational Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY).

Materials And Methods: A total of 4180 infants were randomly assigned to receive the HibMenCY at the ages of 2, 4, 6, and 12 to 15 months or the licensed Hib tetanus toxoid conjugate vaccine (ActHIB) at 2, 4, and 6 months and Hib conjugated to N meningitidis outer membrane protein (PedvaxHIB) at 12 to 15 months.

Measurement of functional anti-meningococcal serogroup a activity using strain 3125 as the target strain for serum bactericidal assay.

Functional anti-N. meningitidis serogroup A (MenA) activity in human serum is detected by serum bactericidal assay (SBA), using either rabbit (rSBA) or human (hSBA) complement, with F8238 as the recommended MenA SBA target strain. However, the F8238 strain may not be optimal for this purpose because, as we show here, it expresses the L11 immunotype, whereas most MenA invasive strains express the L(3,7)9 or L10 immunotype.

Evaluation of pneumococcal polysaccharide immunoassays using a 22F adsorption step with serum samples from infants vaccinated with conjugate vaccines.

The history of the pneumococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) is characterized by a continuous search for increased specificity. A third-generation ELISA that uses 22F polysaccharide inhibition has increased the specificity of the assay, particularly at low antibody concentrations. The present work compared various 22F ELISAs and non-22F ELISAs.

Pneumococcal Haemophilus influenzae protein D conjugate vaccine induces antibodies that inhibit glycerophosphodiester phosphodiesterase activity of protein D.

Haemophilus influenzae outer membrane protein D (PD) is a glycerophosphodiester phosphodiesterase (GlpQ) activity-possessing virulence factor and a promising vaccine antigen, providing 35.3% efficacy against acute otitis media caused by nontypeable H. influenzae (NTHI) when it was used as a carrier protein in a novel pneumococcal PD conjugate (Pnc-PD) vaccine.

Systematic targeted mutagenesis of Brucella melitensis 16M reveals a major role for GntR regulators in the control of virulence.

In order to identify transcriptional regulators involved in virulence gene control in Brucella melitensis, we generated a collection of 88 mutants in the AraC, ArsR, Crp, DeoR, GntR, IclR, LysR, MerR, RpiR, and TetR families of regulators. This collection was named LiMuR (library of mutants for regulators). We developed a method to test several mutants simultaneously in one animal in order to identify those unable to survive.

Brucella pathogenesis, genes identified from random large-scale screens.

Pathogenicity islands, specialized secretion systems, virulence plasmids, fimbriae, pili, adhesins, and toxins are all classical bacterial virulence factors. However, many of these factors, though widespread among bacterial pathogens, are not necessarily found among bacteria that colonize eukaryotic cells in a pathogenic/symbiotic relationship. Bacteria that form these relationships have developed other strategies to infect and grow in their hosts.

Identification of a quorum-sensing signal molecule in the facultative intracellular pathogen Brucella melitensis.

Brucella melitensis is a gram-negative alpha2-proteobacterium responsible for abortion in goats and for Malta fever in humans. This facultative intracellular pathogen invades and survives within both professional and nonprofessional phagocytes. A dichloromethane extract of spent culture supernatant from B.

Yersinia enterocolitica as a vehicle for a naked DNA vaccine encoding Brucella abortus bacterioferritin or P39 antigen.

Brucella is a facultative intracellular parasite that causes brucellosis in animals and humans. The protective immune response against Brucella involves both humoral and cell-mediated immunity. In previous studies, we demonstrated that the T-dominant Brucella antigens bacterioferritin (BFR) and P39 administered either as CpG adjuvant recombinant proteins or as naked-DNA plasmids induced a specific Th1-biased immune response in mice.