Meningococcal Infections
Conditions
Keywords
Meningococcal Vaccines, Neisseria Meningitidis, Factor H-binding Protein
Brief summary
This study will investigate the breadth of protection against meningococcal disease in humans immunized with a newly FDA approved meningococcal B vaccine, trade name Trumenba® manufactured by Pfizer Vaccines. As a secondary goal the investigators will investigate underlying mechanisms by which human anti-FHbp antibodies elicit complement-mediated bactericidal activity.
Detailed description
Neisseria meningitidis causes meningitis and severe infections of the blood stream. The incidence of serogroup B meningococcal disease however is too low to conduct a randomized, controlled trial to determine the actual efficacy of the new serogroup B vaccines. Instead vaccine efficacy was inferred from serum bactericidal antibody responses using four test strains. However, because of strain variability of FHbp amino acid sequence (there are more than 800 sequence variants described) and strain variability of FHbp expression, bactericidal data on only four strains are unlikely to be sufficient to predict the actual strain coverage by the vaccine. There also are gaps in knowledge about the underlying mechanisms by which human antibodies to FHbp elicit complement mediated bactericidal activity. For example, binding of FH to FHbp is specific for human FH. Therefore in vaccinated humans the vaccine antigen is expected to form a complex with FH right after immunization. The investigators' hypothesis is that binding of human FH to the vaccine antigen skews the antibody repertoire to FHbp epitopes located outside of the FH combining site. The resulting antibodies would be expected not to inhibit binding of FH to the bacteria. This hypothesis will be investigated in Trumenba-immunized humans as part of studies in Aim 1 (and in future studies of recombinant human anti-FHbp Fabs that will be enabled by obtaining DNA from individual B cells, described in Aim 2).
Interventions
BIOLOGICALTrumenba Vaccine (Wyeth/Pfizer Pharmaceuticals)
All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule.
Sponsors
University of Massachusetts, Worcester
UCSF Benioff Children's Hospital Oakland
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults in the following risk groups: physicians, nurses, respiratory therapists, microbiology laboratory personnel working at UCSF Benioff Children's Hospital Oakland or the University of Massachusetts Medical School as well as medical students attending accredited U.S. medical schools * Able to comprehend and follow all required study procedures * In good health as determined by a brief medical history * For females of child bearing age a negative urine pregnancy test will be required
Exclusion criteria
* Are not in the risk groups summarized above * Have not given or are unable to give written informed consent to participate in the study * Females of child bearing potential who are pregnant, or planning on becoming pregnant during the study period. * Persons with a past history of having Guillain-Barré Syndrome (GBS), or a family history of GBS in a parent or sibling. * Persons with presence or suspected presence of serious chronic disease including but not limited to: chronic cardiac disease, autoimmune disease, diabetes, hepatitis B/C, HIV, progressive neurological disease or seizure, leukemia, lymphomas, or neoplasm. * Have participated in any other investigational drug or received any other vaccine within the last 30 days. * Received a dose of a meningococcal serogroups A, C, Y, W conjugate vaccine within the previous 30 days or wish to receive a dose of this vaccine during the six month study period. * Have a history of anaphylactic shock, asthma, urticaria or other allergic reaction after previous dose of Trumenba * Have experienced fever (oral temperature above 38.0°C) within the past 3 days or are suffering from a present acute infectious disease * Are planning to leave the area of the study site before the end of the study period * Have obesity (BMI higher than 33); or 11. * With any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Breadth of Protective Activity of Serum Anti-FHbp Antibody Responses of Adults Immunized With Trumenba Vaccine as Assessed by Serum Bactericidal Titers | 18 months | Determine the percentage of subjects achieving serum bactericidal titers of 1:4 or greater in serum obtained 1 month after doses 2 and 3 as measured against a panel of 15 genetically diverse meningococcal strains. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibody Repertoire to FHbp | 1 year | Determine the percentage of recombinant anti-FHbp Fabs isolated from B cells of each subject that react with 3 FHbp amino acid sequence variants representative of FHbp variant groups 1, 2 and 3 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open Label: MenB-FHbp Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals)
Trumenba Vaccine (Wyeth/Pfizer Pharmaceuticals): All subjects will receive three doses of a Trumenba, a U.S.-licensed meningococcal vaccine. Each 0.5 mL dose contains 60 micrograms of each FHbp variant (total of 120 micrograms of protein), 0.018 mg of PS80 and 0.25 mg of Al³+ as AlPO4 in 10 mM histidine buffered saline at pH 6.0. Trumenba is administered as a three dose series (0.5 mL each) according to a 0-, 2-, and 6-month schedule. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Open Label: MenB-FHbp |
|---|---|
| Age, Continuous | 40 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 1 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Breadth of Protective Activity of Serum Anti-FHbp Antibody Responses of Adults Immunized With Trumenba Vaccine as Assessed by Serum Bactericidal Titers
Determine the percentage of subjects achieving serum bactericidal titers of 1:4 or greater in serum obtained 1 month after doses 2 and 3 as measured against a panel of 15 genetically diverse meningococcal strains.
Time frame: 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Label: MenB-FHbp | Breadth of Protective Activity of Serum Anti-FHbp Antibody Responses of Adults Immunized With Trumenba Vaccine as Assessed by Serum Bactericidal Titers | 93 percentage of participants |
Secondary
Antibody Repertoire to FHbp
Determine the percentage of recombinant anti-FHbp Fabs isolated from B cells of each subject that react with 3 FHbp amino acid sequence variants representative of FHbp variant groups 1, 2 and 3
Time frame: 1 year
Population: This was an exploratory objective requiring new technology. It was done on 0/17 subjects because of technical limitation.