Immunogenicity of a U.S.-Licensed Meningococcal Serogroup B Vaccine (Trumenba) in Adults at Increased Risk of Meningococcal Disease Because of Occupational Exposure
Phase: PHASE4
Conditions: Meningococcal Infections
Sponsor: UCSF Benioff Children's Hospital Oakland

 
Immunogenicity of a U.S.-Licensed Meningococcal 
Serogroup B Vaccine (Trumenba) in Adults at Increased 
Risk of Meningococcal Disease Because of Occupational 
Exposure   
 
NCT02569632 
Document Date: 11/14/19 
 

 
2
Title: Immunogenicity of a U.S.-licensed meningococcal serogroup B vaccine 
(Trumenba) in adults at increased risk of meningococcal disease because of 
occupational exposure 
 
 
I. Specific Aims 
In October 2014, the FDA approved the first meningococcal B vaccine in the 
United States for persons 10 to 25 years 
(http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm420998.htm). The 
new vaccine (trade name “Trumenba®”, Meningococcal Group B Vaccine), is 
manufactured by Pfizer Vaccines (Package insert, Appendix A). The antigens consist of 
two Factor H binding proteins (FHbp) expressed as recombinant lipoproteins (referred 
to herein as “Trumenba”).  
For over a decade, our laboratory has been investigating mechanisms by which 
FHbp vaccination confers protection against meningococcal disease using mouse and, 
more recently, non-human primate models. Neisseria meningitidis, however, is a strictly 
a human pathogen, and large gaps exist on understanding the basis of human immunity 
to FHbp.  The recent licensure of the Trumenba vaccine in the U.S. provides an 
opportunity to investigate the breadth of protection against meningococcal disease in 
humans immunized with this new vaccine. As a secondary goal we will investigate 
underlying mechanisms by which human anti-FHbp antibodies elicit complement-
mediated bactericidal activity. The results may form the basis of a future NIH grant 
application. This pilot study will be funded by existing funds in research accounts at 
CHORI and, therefore, will be independent of commercial influence. 
 
Aim 1.  Characterize the breadth of protective activity of serum anti-FHbp 
antibody responses of adults immunized with the Trumenba vaccine.  During 
studies done by the manufacturer for licensing of this vaccine, the breadth of protection 
was defined by serum bactericidal assays using only four test strains (Trumenba 
Package Insert, Appendix A). There are more than 750 FHbp amino acid sequence 
variants in the public database. Because of strain variability in FHbp amino sequence 
and in FHbp expression, the results of testing bactericidal activity against only four 
isolates is unlikely to define the true breadth of protection. Therefore, in Aim 1, we will 
enroll 13 healthy adults who will be immunized with three doses of Trumenba vaccine at 
the recommended 0, 2 and 6 months schedule. We will only include adults with 
increased risk to o exposure to N. meningitidis such as microbiologist, physicians or 
nurses since they are at higher risk of meningococcal disease than the general 
population. Therefore, these persons have the most potential benefit from vaccination. 
Sera will be obtained before and after vaccination and will be assayed for IgG antibody 
responses to FHbp by ELISA, for bactericidal activity against a panel of genetically 
diverse meningococcal strains, and for the ability to inhibit binding of human Factor H 
(FH) to FHbp. FH is a complement down-regulator, which is present in high 
concentrations in serum. In immunized mice, the ability of anti-FHbp antibodies to inhibit 
binding of FH to the bacteria contributed to the breadth of bactericidal activity (with less 
bound FH, the bacteria became more susceptible to complement-mediated bactericidal 
activity)1,2. However, we don’t know whether the anti-FHbp antibody repertoire of 
immunized humans blocks FH binding. 

 
 
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Aim 2.  Define the antibody repertoire to FHbp. The antibodies to FHbp present in 
sera represent the products of multiple B cell clones. Because sera contain a mixture of 
antibodies with different epitope specificities, it is difficult to investigate antibody 
repertoire (i.e., FHbp epitopes recognized by the antibodies) in serum. Therefore, we 
will obtain an additional sample of blood from a sub-set of consenting subjects 7 to 10 
days after vaccine dose 3 for isolation of peripheral blood mononuclear cells (PBMCs). 
The cells will be sorted to obtain individual B cells, which will be frozen for future studies 
that will use PCR to clone the heavy and light chain immunoglobulin variable region 
genes encoding anti-FHbp antibodies. The genes will be used to prepare recombinant 
anti-Fabs (antibody fragments expressing the antigen binding site). These studies are 
labor intensive and will likely require additional funding. Having available stored 
individual B cells from Trumenba-vaccinated humans will be helpful to secure the 
extramural support for a human anti-FHbp Fab project. 
 
II. Background 
Neisseria meningitidis causes meningitis and severe infections of the blood 
stream.  Despite antibiotic treatment mortality rates range from 5 to 20% and 
approximately 20% of survivors are left with permanent sequelae such seizures, 
deafness or limb amputations3,4. The highest incidence of disease is in the first year of 
life with a secondary peak in adolescents and young adults. Nearly all disease in the 
U.S. is caused by strains with capsular serogroups C, Y or B. Currently, meningococcal 
quadrivalent A, C, Y, and W polysaccharide-protein conjugate vaccination is 
recommended for all adolescents in the U.S.  Vaccination is also recommended for 
infants and children <11 years of age and for adults over 20 years who are at increased 
risk of meningococcal disease because of underlying medical conditions (i.e., 
complement deficiency, hypo-splenic function including sickle cell disease, or HIV 
infection) 5, or increased risk of exposure to the organism such as from travel to areas of 
the world with epidemic meningococcal disease, exposure to outbreaks, or occupational 
exposure. Occupation exposure includes clinical and research microbiologists who are 
at more than a 100-fold greater risk of meningococcal disease compared to the general 
population 6-9. The Advisory Committee on Immunization Practices (ACIP) has not yet 
completed formulation of recommendations for use of the new meningococcal 
serogroup B vaccine (recommendations will be voted on at the next meeting in February 
35-27, 2015). However, at the October 2014 ACIP meeting, the group was considering 
a broad recommendation for vaccination of all persons 10 years of age or older who are 
in high risk groups for which meningococcal conjugate vaccination currently is 
recommended (http://www.cdc.gov/vaccines/acip/meetings/meetings-info.html). 
Recommendations also may be extended to all teenagers and college-age students. 
The incidence of serogroup B meningococcal disease was too low to conduct a 
randomized, controlled trial to determine the actual efficacy of the new Trumenba 
vaccine. Instead vaccine efficacy was inferred from serum bactericidal antibody 
responses using four test strains. Approximately 80% to 90% of persons immunized had 
four-fold or greater increases in bactericidal titer, which were defined as protective 
responses (Apendix A, Trumenba Package Insert). However, because of strain 
variability of FHbp amino acid sequence (there are more than 750 sequence variants 

 
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described) and strain variability of FHbp expression10, 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. Binding of 
complement FH by FHbp down-regulates complement activation onto the pathogen’s 
surface. In sera from immunized mice, serum anti-FHbp antibodies inhibit binding of FH 
to the bacterial surface. With less bound FH, the bacteria becomes more susceptible to 
bactericidal activity 1,2.  However, binding of FH to FHbp is specific for human FH11 . 
Therefore in vaccinated humans the vaccine antigen is expected to form a complex with 
FH right after immunization. Our hypothesis, supported by data from studies of other 
FHbp antigens in a human FH transgenic mouse model12,13 14,15 (see Appendix B), 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).  
 
III. PRELIMINARY STUDIES AND PROGRESS REPORT 
In preliminary studies we used a previously characterized human Factor H 
transgenic BALB/c mouse line16 to investigate the effect of human FH on 
immunogenicity of a FHbp-containing vaccine (4CMenB) licensed by Novartis in 
Europe, Canada and Australia15 (Appendix B). Our most important findings were that, 
compared with wild-type mice whose mouse FH doesn’t bind to FHbp, the transgenic 
mice had lower serum IgG anti-FHbp antibody responses, and lower serum bactericidal 
antibody responses against a group B strain with all of the antigens mismatched to the 
4CMenB vaccine except FHbp. The mechanism responsible for the lower FHbp 
immunogenicity in the transgenic mice is not known.  FHbp is relatively sparsely 
exposed on many meningococcal strains 10. In previous studies a critical determinant of 
anti-FHbp bactericidal activity was the ability for low-level C3b deposited by activation of 
the classical pathway to be amplified by the alternative pathway 1, which was enhanced 
if the anti-FHbp antibodies inhibited binding of FH to FHbp 1. We found that while the 
serum anti-FHbp antibodies elicited by 4CMenB in wild-type mice inhibited binding of 
FH to FHbp, the corresponding antibodies elicited in human FH transgenic mice 
enhanced FH binding. The lack of FH inhibition in the transgenic mice suggested that 
the anti-FHbp antibody repertoire was skewed towards FHbp epitopes outside of the FH 
combining site. We do not however understand, however, the molecular basis for the 
FH enhancement. Conceivably, binding of antibodies to certain FHbp epitopes outside 
of the FH combining site resulted in conformational changes in FHbp that rendered the 
molecule more accessible for FH binding.  
 
IV.  EXPERIMENTAL DESIGN AND METHODS  
 
General study design.  This is a pilot study for immunizing 13 healthy adults, ages 18 
to 55 years. The subjects will be from groups at increased risk of meningococcal 
disease because of higher likelihood of exposure to the organism (i.e., microbiologists 

 
 
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and physicians, nurses, respiratory therapists and medical students). All subjects will 
receive three doses of a U.S.-licensed meningococcal vaccine (Trumenba) according to 
the recommended 0, 2 and 6 months after the first dose. 
Three blood samples will be obtained from all 13 subjects. These will be obtained 
immediately before doses 1 (30 ml), and three to six weeks after doses two and three 
(75 ml at each time point).  In subjects that consent for an additional sample, we also 
will obtain a 60 ml blood sample 7-10 days after vaccination dose 3 for isolation of B 
cells. The cells will be used for studies of recombinant anti-FHbp Fabs for investigation 
of antibody repertoire (Aim 2). 
The sera will be assayed for IgG antibody responses to FHbp, bactericidal 
activity against a panel of meningococcal strains, and other studies of meningococcal 
immunity such as inhibition of binding FH to FHbp, or passive protection against 
meningococcal bacteremia in an infant rat model 17.  
The meningococcal B vaccine is approved in the U.S. for individuals 10 to 25 years 
because the data provided by the manufacturer to the FDA supporting safety and 
effectiveness only was limited to that age group. Most persons who are at increased risk 
of meningococcal disease because of occupational exposure to the bacteria are older 
than 25 years. Our study will include individuals with ages 18 to 55 years, which includes 
persons older than 25 years, an age group considered as “off label” use. There is no 
reason to anticipate that the vaccine will be less effective or less safe in otherwise healthy 
persons ages 26 to 55 compared to 10 to 25 years. As described above (II. Background), 
the U.S. Advisory Committee on Immunization Practices (ACIP) is considering an 
expanded age range that includes 26 to 55 years for vaccination of persons at increased 
risk of meningococcal disease. Also, in Europe, another meningococcal B vaccine called 
Bexsero, which contains a similar FHbp antigen as in the meningococcal B vaccine being 
tested in our study (Trumenba), is licensed for persons up to age 55 years. Detailed safety 
data in our study will be limited to collection of information on notable severe or serious 
adverse events only, which will be obtained at the time of each scheduled visit.  
Patient selection: Healthy adults, ages 18 to 55 years, of either sex will be recruited 
from physicians, nurses, respiratory therapists or microbiology laboratory personnel 
working at the UCSF Benioff Children Hospital Oakland. Medical students attending 
UCSF or other accredited U.S. medical schools also will be eligible. 
 
Inclusion criteria: Individuals eligible to be enrolled in the study are those: 1. in the risk 
groups summarized above (see Patient Selection); 2. able to comprehend and follow all 
required study procedures; 3. willing and able to sign an informed consent form; 4. 
available for all the visits scheduled in the study; 5. are in good health as determined by a 
brief medical history; and 6. for females of child bearing age a negative urine pregmancy 
test will be required .  Note, according to the FDA, Trumenba should be used in 
pregnancy only when clearly indicated.  While microbiologists working with serogroup B 
meningococci might be in that category because of their high risk of disease, in a clinical 
study it is prudent not to enroll women who are pregnant or planning to become pregnant 
during the six months required for completing three doses of the vaccine. 
 
Exclusion criteria: Individuals who should not be enrolled in the study are those: 1, who 
are not in the risk groups summarized above; 2, who have not given or are unable to give 

 
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written informed consent to participate in the study; 3, females of child bearing potential 
who are pregnant, or planning on becoming pregnant during the study period. 4, Persons 
with a past history of having Guillain-Barré Syndrome (GBS), or a family history of GBS 
in a parent or sibling, will be excluded from participation in this study. 5. 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. 6. Persons who 
have participated in any other investigational drug or received any other vaccine within 
the last 30 days.7. Persons who 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;  7. a history of anaphylactic shock, asthma, urticaria or 
other allergic reaction after previous dose of Trumenba;  8. who have experienced fever 
(oral temperature above 38.0C) within the past 3 days or are suffering from a present acute 
infectious disease; 9. who are planning to leave the area of the study site before the end of 
the study period; 10. who have obesity (BMI higher than 30); or 11. with any condition 
which, in the opinion of the investigator, might interfere with the evaluation of the study 
objectives. 
 
 
Procedures 
 
Trumenba Meningococcal Group B Vaccine (Wyeth/Pfizer Pharmaceuticals). The 
vaccine is a suspension for intramuscular injection in 0.5 mL single-dose prefilled 
syringes. 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. Table 1 summarizes the 
various visits and procedures that will be performed during the 7-month study. 
 
 
 

 
 
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Table 1: Trumenba Meningococcal Group B vaccine study: Summary of visits and 
events (total of 13 subjects) 
 
Activity 
Day 0 
2 months 
(60 to 80 
day) 
3 months 
(3-to 6 
weeks Post 
Dose 2) 
6 months 
7 to 10 Days 
Post Dose 3 
7 months 
(3 to 6 
Weeks Post 
Dose 3) 
Screen for 
inclusion and 
exclusion criteria 
X 
X 
 
X 
 
 
Informed written 
consent 
X 
 
 
 
X (Review for 
obtaining 
optional blood 
sample) 
 
Targeted physical 
exam and 
medical history 
X 
X 
 
X 
 
 
Blood draw 
30 ml 
(Sample 
A) 
 
75 ml 
(Sample B) 
 
60 ml* 
(Sample D) 
75 ml 
(Sample C) 
Type of blood 
sample 
Serum 
only 
 
Serum 
only 
 
*Anti-
coagulated for 
PBMC) 
Serum only 
Immunization 
X 
X (Dose 
2) 
 
X (Dose 3) 
 
 
Collect 
information on 
SAE and severe 
reactions 
 
X 
X 
X 
X 
X 
Note, total volume of serum for all subjects having three blood samples is 180 ml; for 
those providing optional blood sample, 240 ml. 
 
Blood specimens.  Blood specimens will consist of 30 ml obtained immediately before 
immunization with dose 1, and 75 ml obtained three to six weeks after dose 2 and dose 
3 (total of 3 blood draws, designated A, B, and C, in all 13 subjects). Sera will be 
separated and stored frozen for serologic assays. In consenting subjects, an additional 
60 ml of anti-coagulated blood (Sample D) will be obtained 7 to 10 days after vaccine 
dose 3 for isolation of individual B cells for preparation of recombinant anti-FHbp Fabs 
(Aim 2). 
 
Safety and immunization.  On enrollment, subjects will undergo a brief history and 
directed physical exam. Subjects who meet all inclusion criteria and no exclusion criteria 
will receive an immunization at visit 1 (study day 0), visit 2 (2 months; range 40 to 80 
days) and visit 4 (6 months, range 180 to 240 days). Visits 3 and 6 will consist of blood 
draws only at 3 to 6 weeks after doses 2 and 3, respectively. At each visit information 
will be obtained on notable adverse events occurring within 7 days of vaccination, and 

 
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any serious adverse event (SAE) occurring during the 7-month study period. The FDA 
defines a SAE as “Death, life-threatening, or requiring hospitalization (not necessarily 
caused by the vaccine). 
  
Immunologic assessment. Sera will be assayed by ELISA for titers of anti-FHbp 
antibodies and the ability of the antibodies to inhibit or enhance binding of FH to FHbp.  
Complement-mediated bactericidal activity will be measured with human complement 
using a panel of diverse strains. Other assays for meningococcal immunity may also be 
performed such as antibody binding to live bacteria measured by flow cytometry, and 
the ability of the serum antibodies to confer passive protection in an infant rat 
bacteremia model.  All of these methods have been performed routinely in our 
laboratory for more than a decade (see for example, citations 1,2,18,19 ). All of the assays 
using live meningococci will be performed in a BL2+ facility using protocols approved by 
the CHORI Institutional Biosafety Committee (IBC).  
 
Data Safety Monitoring Plan  
The study is slightly above minimal risk because the age group 26 to 55 years is 
considered currently “off-label” for use of an FDA-approved vaccine for the age group 
10 to 25 years.  No serious adverse events are anticipated related to vaccination. The 
other study procedures include three to four blood draws over seven months from 
healthy adults in which a total of less than 240 ml of blood will obtained (approximately 
half of the volume that can be safely drawn at a single blood donation at the blood 
bank).   
 
ADVERSE REACTIONS 
 
Clinical Trials Experience: (From the package insert). The safety of Trumenba was 
evaluated in 4,282 subjects 11 through 25 years of age in 7 clinical studies (4 
randomized controlled and 3 supportive non-controlled studies) conducted in the US, 
Europe, and Australia. A total of 4,250 adolescents (11 through 18 years of age) and 32 
adults (19 through 25 years of age) received at least one dose of Trumenba. A total of 
1,004 subjects 11 through 25 years of age in the control groups received saline placebo 
and/or one of the following vaccines: Human Papillomavirus Quadrivalent (Types 6, 11, 
16, and 18) Vaccine, Recombinant [HPV4]; a non-US licensed tetanus toxoid, reduced 
diphtheria toxoid, acellular pertussis and inactivated polio virus vaccine; or Tetanus 
Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Sanofi 
Pasteur Ltd.). The safety evaluation in the 7 studies included an assessment of: (1) 
solicited local and systemic reactions, and (2) use of antipyretic medication after each 
vaccination 
 
Solicited Local and Systemic Adverse Reactions: The Trumenba vaccine was 
generally well-tolerated although most patients (85-93%) experienced injection site 
reactions; fatigue (43-64%), headache (35-57%), muscle pain (31-42%), or chills (16-
30%). These reactions were usually of mild to moderate severity and transient. In 
general the rates of these reactions were only slightly higher than those of subjects 

 
 
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receiving comparator control vaccines (including a U.S.-licensed quadrivalent human 
papilloma vaccine).  
 
Serious Adverse Events: Among the 4 controlled studies (Trumenba N=2557, control 
N=1004), serious adverse events were reported in 44 (1.7%) subjects who received 
Trumenba and 16 (1.6%) control subjects, for individuals who received at least one 
dose.  
 
Non-serious Adverse Events: Among the 4 controlled studies (Trumenba N=2557, 
control N=1004), AEs that occurred within 30 days of vaccination were reported in 739 
(28.9%) subjects who received Trumenba and 313 (31.2%) subjects in the control 
group, for individuals who received at least one dose. AEs that occurred at a frequency 
of at least 2% and were more frequently observed in subjects who received Trumenba 
than subjects in the control group were injection site pain and headache. 
 
In summary, in this study we will vaccinate healthy adults with a FDA-approved vaccine. 
The subjects enrolled will have increased risk of acquiring meningococcal serogroup B 
disease because of occupational exposure. The approved age group for Trumenba is 
10 to 25 years, while the proposed age group in our study is 18 to 55 years, which 
includes off-label use in subjects over 25 years. However, most persons with 
occupational exposure to N. meningitidis are over 25 years of age and there is no 
reason to expect that the vaccine effectiveness or safety will be different in this older 
age group than in the group 18 to 25 years. Also at discussions at the Advisory 
Committee on Immunization Practices (October 30, 2014 meeting), they intend to 
harmonize their recommendations for Trumenba vaccination to be consistent with 
current recommendations for use of meningococcal A,C,Y,W conjugate vaccine, which 
includes the age group up to 55 years 
(http://www.cdc.gov/vaccines/acip/meetings/meetings-info.html).  
 
Any serious adverse events will be promptly reported to the IRB. In addition, all changes 
in protocol procedures will be submitted for review and approval of the IRB. 
  
V. BIOSTATISTICAL DESIGN AND ANALYSIS 
 
Sample size and justification. 
 
Immunologic analyses. The proposed study is a pilot study and is descriptive with the 
following objectives. 1.  Characterization of the functional activity of serum anti-FHbp 
antibody responses of adults immunized with a newly licensed meningococcal FHbp 
vaccine, 2, Obtain individual B cells for preparation and characterization of human 
recombinant anti-FHbp Fabs. The proposed 13 immunized adults is a convenience 
sample and is based on the number of subjects that we can practically enroll in a pilot 
study with the resources available. Based on published data and data in the package 
insert, we expect that 80% to 90% of subjects will have 4-fold or greater increases in 
serum bactericidal activity (comparing titers after dose 3 to those present before dose 1) 
when measured against four test strains similar those used by the manufacturer in pre-

 
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licensure studies.  We expect that by testing additional test strains expressing FHbp 
variants with less cross-reactivity with the vaccine antigens, and/or lower expression of 
FHbp, that protective responses will be lower (ranging from 30 to 50% with 4-fold or 
greater increases in titer).    
 
Summary statistics.  The respective bactericidal titers at each visit will be 
logarithmically transformed (base 10).  For each visit, GMT’s and associated 95% 
confidence intervals will be computed by exponentiation of the corresponding means 
and 95% confidence limits calculated on the logarithmic scale.  Titers below the limit of 
detection will be assigned values half of the lower limit.  The percentages of subjects 
developing protective bactericidal titers of 1:4 or greater, or showing four-fold or greater 
increases in serum bactericidal activity, will be tabulated for each visit along with the 
respective 95% confidence intervals. 
 
Safety. The frequency and percentage of subjects reporting serious adverse events, 
and severe local or systemic adverse events, or early withdrawal from study will be 
tabulated. 
  
VI. HUMAN SUBJECTS  
 
a) Subject Population: 
13 adults, ages 18 to 55 years, will be immunized with the Trumenba vaccine. We will 
make an effort to include persons of different race (particularly African Americans) and 
both men and women. In our pilot study, we are interested in defining antibody  
responses of healthy persons with increased risk primarily from occupational exposure. 
Therefore persons at increased risk because of underlying diseases known to affect 
immune responses (such as sickle cell disease), or with complement deficiencies will be 
excluded. Pregnant women also will be excluded since the safety of the vaccine has not 
been established during pregnancy.  Children <18 years of age will be excluded 
because this study focuses on responses of healthy adults at increased risk because of 
occupational exposure, currently the group with the greatest benefit from vaccination. 
 
 
 

 
 
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Study Title: Immunogenicity of a U.S.-licensed meningococcal serogroup B vaccine 
(Trumenba) in adults at increased risk of meningococcal disease because of 
occupational exposure. 
Total Planned Enrollment: 13 
TARGETED/PLANNED ENROLLMENT: Number of Subjects 
Ethnic Category 
Sex/Gender 
Females 
Males 
Total 
Hispanic or Latino 
2 
1 
3 
Not Hispanic or Latino 
5 
5 
9 
Ethnic Category Total of All Subjects* 
7 
6 
13 
Racial Categories 
 
American Indian/Alaska Native 
0 
0 
0 
Asian 
2 
2 
4 
Native Hawaiian or Other Pacific 
Islander  
0 
0 
0 
Black or African American  
1 
1 
2 
White 
4 
3 
6 
Racial Categories: Total of All 
Subjects * 
7 
6 
13 
 
*The “Ethnic Category Total of All Subjects” must be equal to the “Racial Categories 
Total of All Subjects.” 
 
b) Sources of material: 
 
 Blood specimens from living human subjects. The material will be obtained 
specifically for research purposes. 
 
c) Recruitment plans:  
Subjects will be recruited from hospital employees and from medical students.  
Potential volunteers will have the study explained to them verbally by the study 
coordinator, research nurse or physician.   If they express interest, they will be given an 
“informed consent form.” which will inform them further about the purpose of this study, 
what is known about the vaccine that will be administered, and the blood sampling 
procedures that will be done should they decide to enroll in the study. The form also will 
contain information on the risks and benefits of participating.  They will be asked to read 

 
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this form carefully and ask questions before deciding to enroll. Prospective volunteers 
may take as much time as they like to make up their minds.  They will be informed that 
participation is voluntary.  Should they decide not to participate, they will be informed 
that they may receive the vaccine outside the study by going to their physician or 
employee health. 
 
d) Potential risks: 
  Vaccine-related risks include local reactions such as erythema, induration, pain 
at injection site, which occur in up to 50% of subjects. Systemic reactions such as fever, 
chills, malaise nausea, headache, fatigue, myalgia or arthralgia occur in approximately 
90% of immunized persons.  These side effects are usually of mild severity and last less 
than 1 or 2 days and are similar to side effects experience with most vaccines.  Blood 
drawing may cause some discomfort, local bruising, and rarely, infection.   Some donors 
may experience transient light-headedness.  The total volume of blood obtained over 
the six months duration of this study (<200 ml) is less than taken on one occasion 
during routine donation of a unit of blood at a blood bank.   
 
e) Protection against risks: 
 
 
Subjects will have a targeted physical examination performed and medical 
history to ensure that they are in good health. Subjects who meet all inclusion criteria 
and no exclusion criteria will have a 30 ml blood specimen obtained. They will then 
receive the immunization. Immunization will be repeated at months 2 and 6.  Blood 
samples (75ml) will be obtained three to six weeks after doses 2 and 3.  Optionally, a 
fourth blood sample (60 ml) will be obtained 7 to 10 days after dose 3. Should light-
headedness occur during or immediately after blood drawing, subjects will be placed in 
a reclining position with legs elevated, and provided supplemental oral hydration, such 
as juice. The procedures will be performed in a facility designed for performing clinical 
studies by a licensed nurse or physician. Epinephrine will be available should 
anaphylaxis occur. These procedures should minimize risk of the study.   
 
f) Confidentiality of data collected during the study will be protected. Consent forms, 
results of physical examinations and medical histories, will be maintained in a secure 
file cabinet within the PI’s office. Identity of the subjects will not be revealed during 
presentations or publications of the results. 
 
 
 

 
 
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g) Potential benefits: 
The vaccine confers protection against meningococcal disease caused by 
serogroup B strains and potentially also protects against some strains from serogroups 
A, C, Y and W.  Serogroup B strains currently account for approximately 40% of cases 
of disease in the U.S.  
The results will increase our understanding of the breadth of protection elicited by 
this new serogroup B vaccine and the functional basis of vaccine-induced anti-FHbp 
immunity to group B meningococci. The results could lead to better public health 
recommendations for use of the vaccine and, eventually, to better and safer vaccines. 
The data will establish whether there is a relationship between antibody functional 
activity ability of the anti-FHbp antibodies to either enhance or block hFH binding to the 
bacteria. 
 
VII. NEED FOR THE PCRC 
 
Use of the PCRC facilities to conduct research visits has been requested and 
tentative approval given. 
 
 
PROJECTED USE TABLE 
 
2014 
 
2015 
 
2016 
 
2017 
 
2018 
Number of enrolled subjects per year 
 
13 
 
 
 
Number of completed subjects per 
year 
 
13 
 
 
 
Total inpatient days per year 
 
0 
 
 
 
Total outpatient days per year 
 
60 to 72 
 
 
 
Total scatter nurse visits per year 
 
0 
 
 
 
Total scatterbed days per year 
 
0 
 
 
 
 
Total Number of Subjects to be Enrolled 
13 
Total Number of Subjects to Complete Study 10-12 
 
VIII. REFERENCES 
 
1. 
Giuntini S, Reason DC, Granoff DM. Complement-mediated bactericidal activity of anti-factor H binding 
protein monoclonal antibodies against the meningococcus relies upon blocking factor H binding. Infection and 
immunity 2011;79:3751-9. 
2. 
Konar M, Granoff DM, Beernink PT. Importance of inhibition of binding of complement Factor H for serum 
bactericidal antibody responses to meningococcal Factor H-binding protein vaccines. J Infect Dis 2013;208:627-36. 
3. 
Fellick JM, Sills JA, Marzouk O, Hart CA, Cooke RW, Thomson AP. Neurodevelopmental outcome in 
meningococcal disease: a case-control study. Arch Dis Child 2001;85:6-11. 
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Dodge PR, Scaer M, Holmes SJ, Pomeroy SL, Feigin RD. Psychometric testing in bacterial meningitis: 
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IX. 
RELATED OTHER SUPPORT.  None.   
 
X. 
Appendix 
 
A. Trumenba package insert